Reference Citation Analysis: Find an Article, Find a Category, Find a Journal, Find a Scholar

For: Lin JS, Mamlouk O, Selamet U, Tchakarov A, Glass WF, Sheth RA, Layman RM, Dadu R, Abdelwahab N, Abdelrahim M, Diab A, Yee C, Abudayyeh A. Infliximab for the treatment of patients with checkpoint inhibitor-associated acute tubular interstitial nephritis. Oncoimmunology 2021;10:1877415. [PMID: 33643693 PMCID: PMC7872057 DOI: 10.1080/2162402x.2021.1877415] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open

For:	Lin JS, Mamlouk O, Selamet U, Tchakarov A, Glass WF, Sheth RA, Layman RM, Dadu R, Abdelwahab N, Abdelrahim M, Diab A, Yee C, Abudayyeh A. Infliximab for the treatment of patients with checkpoint inhibitor-associated acute tubular interstitial nephritis. Oncoimmunology 2021;10:1877415. [PMID: 33643693 PMCID: PMC7872057 DOI: 10.1080/2162402x.2021.1877415] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open

Number

Cited by Other Article(s)

Guo YX, Yan X, Liu XC, Liu YX, Liu C. Artificial intelligence-driven strategies for managing renal and urinary complications in inflammatory bowel disease. World J Nephrol 2025;14:100825. [DOI: 10.5527/wjn.v14.i1.100825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Revised: 11/29/2024] [Accepted: 12/27/2024] [Indexed: 01/20/2025] Open

Barbir EB, Mohan A, Koirala P, Gutierrez LE, Giesen CD, Lieske JC, Herrmann SM. Biomarker-guided infliximab therapy for immune checkpoint inhibitor-induced acute interstitial nephritis. Nephrol Dial Transplant 2025;40:602-604. [PMID: 39516049 DOI: 10.1093/ndt/gfae257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Indexed: 11/16/2024] Open

Gueutin V, Dalle S, Isnard-Bagnis C, Laparra A, Assad S, Burtey S, Audard V, Belliere J. [Acute kidney injury in cancer patients receiving immune checkpoint inhibitor therapy-shared guidelines of FITC/SFNDT]. Bull Cancer 2025;112:225-235. [PMID: 39643454 DOI: 10.1016/j.bulcan.2024.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 10/05/2024] [Accepted: 11/04/2024] [Indexed: 12/09/2024]

Herrmann SM, Abudayyeh A, Gupta S, Gudsoorkar P, Klomjit N, Motwani SS, Karam S, Costa E Silva VT, Khalid SB, Anand S, Kala J, Leaf DE, Murakami N, Rashidi A, Wanchoo R, Kitchlu A. Diagnosis and management of immune checkpoint inhibitor-associated nephrotoxicity: a position statement from the American Society of Onco-nephrology. Kidney Int 2025;107:21-32. [PMID: 39455026 DOI: 10.1016/j.kint.2024.09.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 09/09/2024] [Accepted: 09/13/2024] [Indexed: 10/28/2024]

Affiliation(s)

Sandra M Herrmann Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA.
Ala Abudayyeh Section of Nephrology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
Shruti Gupta Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA; Department of Medical Oncology, Dana-Farber Cancer Institute. Harvard Medical School, Boston, Massachusetts, USA
Prakash Gudsoorkar Division of Nephrology, University of Cincinnati, Cincinnati, Ohio, USA
Nattawat Klomjit Department of Medicine, Division of Nephrology and Hypertension, University of Minnesota, Minneapolis, Minnesota, USA
Shveta S Motwani Department of Medical Oncology, Dana-Farber Cancer Institute. Harvard Medical School, Boston, Massachusetts, USA
Sabine Karam Department of Medicine, Division of Nephrology and Hypertension, University of Minnesota, Minneapolis, Minnesota, USA; Department of Internal Medicine, Division of Nephrology and Hypertension, American University of Beirut, Beirut, Lebanon
Verônica T Costa E Silva Serviço de Nefrologia, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil; Laboratório de Investigação Médica (LIM) 16, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
Sheikh B Khalid Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
Shuchi Anand Department of Medicine (Nephrology), Stanford University, Stanford, California, USA
Jaya Kala Division of Renal Diseases and Hypertension, University of Texas Health Science Center at Houston-McGovern Medical School, Houston, Texas, USA
David E Leaf Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
Naoka Murakami Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
Arash Rashidi Division of Nephrology and Hypertension, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
Rimda Wanchoo Division of Kidney Diseases and Hypertension, Glomerular Center at Northwell Health, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Great Neck, New York, USA
Abhijat Kitchlu Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada

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Strouse J, Chan KK, Baccile R, He G, Louden DKN, Giurcanu M, Singh A, Rieth J, Abdel-Wahab N, Katsumoto TR, Singh N, Rouhani S, Reid P. Impact of steroid-sparing immunosuppressive agents on tumor outcome in the context of cancer immunotherapy with highlight on melanoma: a systematic literature review and meta-analysis. Front Immunol 2024;15:1499478. [PMID: 39737191 PMCID: PMC11682972 DOI: 10.3389/fimmu.2024.1499478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 11/25/2024] [Indexed: 01/01/2025] Open

Abstract

Background

The impact of steroid-sparing immunosuppressive agents (SSIAs) for immune-related adverse events (irAEs) on tumor outcome is not well-known. This systematic review evaluates tumor outcomes for corticosteroid (CS) monotherapy versus CS with SSIA (CS-SSIA) for irAE treatment with a focus on melanoma.

Methods

Search was conducted through 1/5/23 using PubMed, Embase, Cochrane CENTRAL, and Web of Science. We included case series, retrospective/prospective observational studies and interventional clinical trials. Individual-level data was analyzed using KM curves and Cox regression for overall survival (OS) and progression free survival (PFS). Time to SSIA was treated as a time-varying exposure using landmark analysis (landmark timepoint=3 months after irAE) to account for immortal time bias. For group-level data, meta-analysis compared the use of SSIA to No SSIA for irAEs.

Results

Of twenty-two publications with individual-level data, 147 patients with any cancer (57 CS, 90 CS-SSIA) and 65 with melanoma (18 CS, 47 CS-SSIA) underwent landmark analysis. Twenty-two publications underwent group-level evaluation and four were included in the meta-analysis. CS-SSIA versus CS showed higher risk of all-cause mortality and progression (HR 2.75, 95%CI: 1.44-5.27, p<0.01 and HR 1.75, 95%CI: 1.07-2.85, p=0.03, respectively). Melanoma showed worse OS and PFS for CS-SSIA versus CS (HR 5.68, 95%CI: 1.31-24.67, p=0.02 and HR 2.68, 95%CI: 1.12-6.40, p=0.03, respectively). In the meta-analysis of group-level data (n=2558), we found worse OS and PFS for CS-SSIA versus No SSIA (HR 1.58, 95%CI: 1.25; 2.01, p<0.01 and 1.70, 95%CI: 1.25-2.33, p<0.01). Tumor necrosis factor-alpha inhibitors (TNFi) were the most common SSIA. In the melanoma cohort, TNFi had worse OS and PFS versus CS (HR 6.46, 95%CI: 1.43-29.19, p = 0.02 and HR 7.49, 95%CI: 2.29-24.48, p<0.01, respectively). TNFi versus Other SSIAs showed a trend toward worse OS and worse PFS (HR 6.96, 95%CI: 0.90-53.65, p=0.06 and HR 21.5, 95%CI: 2.63-175.8, p<0.01, respectively). Meta-analysis showed a concern for TNFi compared to Other SSIA (HR 1.56, 95%CI: 1.17-2.09, p<0.01 respectively).

Conclusions

While our results raise concern about the effects of CS-SSIA and TNFi for irAE therapy on tumor outcomes, prospective randomized controlled trials are needed to definitively assess the effect of SSIAs on tumor outcomes.

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Barbir EB, Kitchlu A, Herrmann SM. Immune checkpoint inhibitor-associated nephritis-treatment standard. Nephrol Dial Transplant 2024;39:1785-1798. [PMID: 39138117 DOI: 10.1093/ndt/gfae184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Indexed: 08/15/2024] Open

Abstract

Over the last 13 years, the use of immune checkpoint inhibitor (ICI) therapy has grown remarkably, owing to their unprecedented anti-tumor efficacy in certain tumor groups. With increased use of ICIs, we are seeing immune-related adverse events (irAEs) more frequently. Renal irAEs, such as ICI-associated acute kidney injury (ICI-AKI), are reported in 2%-5% of patients treated with ICIs, with acute tubulointerstitial nephritis (ATIN) as the most common histopathologic lesion, though various forms of glomerulonephritis have also been reported. Modifiable risk factors for ICI-AKI include concurrent use of ATIN-associated drugs, like proton pump inhibitors, non-steroidal anti-inflammatory drugs and antibiotics, and dual ICI therapy with both Cytotoxic T-lymphocyte Associated Protein 4 (CTLA-4) and Programmed Cell Death Protein 1 and its ligand (PD1/PDL-1) blockade. Kidney biopsies remain the diagnostic modality of choice, though several promising non-invasive biomarkers, which have not yet been broadly clinically validated have emerged. The treatment of ICI-AKI involves holding ICIs, discontinuation of ATIN-associated drugs and initiation of immunosuppression with corticosteroids as first-line therapy. With prompt treatment initiation, most patients achieve full or partial renal recovery, allowing for re-challenge with ICI. However, a subset of patients will require additional steroid-sparing therapies for corticosteroid-dependent or refractory ICI-AKI. Here we review developments in our understanding of the pathophysiology of ICI-AKI, the approach to diagnosis (with a focus on the emergence of novel diagnostic tools), prognostic factors and the current evidence for establishing treatment standards for ICI-AKI. As the evidence base remains largely retrospective, we identify questions that would benefit from future prospective studies in the diagnosis, management and prognostication of ICI-AKI.

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Cheema PK, Iafolla MAJ, Abdel-Qadir H, Bellini AB, Chatur N, Chandok N, Comondore VR, Cunningham M, Halperin I, Hu AB, Jaskolka D, Darvish-Kazem S, Khandaker MH, Kitchlu A, Sachdeva JS, Shapera S, Woolnough NRJ, Nematollahi M. Managing Select Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitors. Curr Oncol 2024;31:6356-6383. [PMID: 39451777 PMCID: PMC11506662 DOI: 10.3390/curroncol31100473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 10/12/2024] [Accepted: 10/16/2024] [Indexed: 10/26/2024] Open

Affiliation(s)

Parneet K. Cheema William Osler Health System, Brampton, ON L6R 3J7, Canada; (M.A.J.I.); (A.B.B.); (N.C.); (V.R.C.); (A.B.H.); (D.J.); (S.D.-K.); (M.H.K.); (J.S.S.); (N.R.J.W.); (M.N.)
Marco A. J. Iafolla William Osler Health System, Brampton, ON L6R 3J7, Canada; (M.A.J.I.); (A.B.B.); (N.C.); (V.R.C.); (A.B.H.); (D.J.); (S.D.-K.); (M.H.K.); (J.S.S.); (N.R.J.W.); (M.N.)
Husam Abdel-Qadir Women’s College Hospital Research Institute, Toronto, ON M5S 1B2, Canada; Division of Cardiology, Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network, Toronto, ON M5G 2N2, Canada
Andrew B. Bellini William Osler Health System, Brampton, ON L6R 3J7, Canada; (M.A.J.I.); (A.B.B.); (N.C.); (V.R.C.); (A.B.H.); (D.J.); (S.D.-K.); (M.H.K.); (J.S.S.); (N.R.J.W.); (M.N.)
Nazira Chatur Division of Gastroenterology, Faculty of Medicine, Vancouver General Hospital (Sanders), University of British Columbia, Vancouver, BC V5Z 1M9, Canada;
Natasha Chandok William Osler Health System, Brampton, ON L6R 3J7, Canada; (M.A.J.I.); (A.B.B.); (N.C.); (V.R.C.); (A.B.H.); (D.J.); (S.D.-K.); (M.H.K.); (J.S.S.); (N.R.J.W.); (M.N.)
Vikram R. Comondore William Osler Health System, Brampton, ON L6R 3J7, Canada; (M.A.J.I.); (A.B.B.); (N.C.); (V.R.C.); (A.B.H.); (D.J.); (S.D.-K.); (M.H.K.); (J.S.S.); (N.R.J.W.); (M.N.)
Morven Cunningham Toronto Centre for Liver Disease, University Health Network, Toronto, ON M5G 2C4, Canada;
Ilana Halperin Division of Endocrinology, Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada;
Anne B. Hu William Osler Health System, Brampton, ON L6R 3J7, Canada; (M.A.J.I.); (A.B.B.); (N.C.); (V.R.C.); (A.B.H.); (D.J.); (S.D.-K.); (M.H.K.); (J.S.S.); (N.R.J.W.); (M.N.)
Diana Jaskolka William Osler Health System, Brampton, ON L6R 3J7, Canada; (M.A.J.I.); (A.B.B.); (N.C.); (V.R.C.); (A.B.H.); (D.J.); (S.D.-K.); (M.H.K.); (J.S.S.); (N.R.J.W.); (M.N.)
Saeed Darvish-Kazem William Osler Health System, Brampton, ON L6R 3J7, Canada; (M.A.J.I.); (A.B.B.); (N.C.); (V.R.C.); (A.B.H.); (D.J.); (S.D.-K.); (M.H.K.); (J.S.S.); (N.R.J.W.); (M.N.)
Masud H. Khandaker William Osler Health System, Brampton, ON L6R 3J7, Canada; (M.A.J.I.); (A.B.B.); (N.C.); (V.R.C.); (A.B.H.); (D.J.); (S.D.-K.); (M.H.K.); (J.S.S.); (N.R.J.W.); (M.N.)
Abhijat Kitchlu Division of Nephrology, Department of Medicine, University Health Network, University of Toronto, Toronto, ON M5G 2C4, Canada;
Jasdip S. Sachdeva William Osler Health System, Brampton, ON L6R 3J7, Canada; (M.A.J.I.); (A.B.B.); (N.C.); (V.R.C.); (A.B.H.); (D.J.); (S.D.-K.); (M.H.K.); (J.S.S.); (N.R.J.W.); (M.N.)
Shane Shapera Department of Medicine, University of Toronto, Toronto, ON M5G 2N2, Canada;
Nicholas R. J. Woolnough William Osler Health System, Brampton, ON L6R 3J7, Canada; (M.A.J.I.); (A.B.B.); (N.C.); (V.R.C.); (A.B.H.); (D.J.); (S.D.-K.); (M.H.K.); (J.S.S.); (N.R.J.W.); (M.N.)
Massey Nematollahi William Osler Health System, Brampton, ON L6R 3J7, Canada; (M.A.J.I.); (A.B.B.); (N.C.); (V.R.C.); (A.B.H.); (D.J.); (S.D.-K.); (M.H.K.); (J.S.S.); (N.R.J.W.); (M.N.)

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Liu X, Guo Y, Pan J, Wu T, Zhao B, Wei S, Jiang W, Liu Y. Nanoparticles constructed from natural polyphenols are used in acute kidney injury. J Mater Chem B 2024;12:8883-8896. [PMID: 39177039 DOI: 10.1039/d4tb00837e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/24/2024]

Affiliation(s)

Xiaohua Liu Henan Science and Technology Innovation Promotion Center, Zhengzhou 450046, China
Yike Guo Department of Pharmacy, Central China Subcenter of National Center for Cardiovascular Diseases, Henan Cardiovascular Disease Center, Fuwai Central-China Cardiovascular Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou 450046, China. Academy of Medical Sciences, Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, Henan, China
Jiangpeng Pan Department of Pharmacy, Central China Subcenter of National Center for Cardiovascular Diseases, Henan Cardiovascular Disease Center, Fuwai Central-China Cardiovascular Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou 450046, China.
Tingting Wu Department of Pharmacy, Central China Subcenter of National Center for Cardiovascular Diseases, Henan Cardiovascular Disease Center, Fuwai Central-China Cardiovascular Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou 450046, China.
Bing Zhao Henan Finance University, Zhengzhou 450046, China
Shuyi Wei Plastic Surgery Department, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, China.
Wei Jiang Department of Pharmacy, Central China Subcenter of National Center for Cardiovascular Diseases, Henan Cardiovascular Disease Center, Fuwai Central-China Cardiovascular Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou 450046, China. Academy of Medical Sciences, Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, Henan, China
Ying Liu Department of Pharmacy, Central China Subcenter of National Center for Cardiovascular Diseases, Henan Cardiovascular Disease Center, Fuwai Central-China Cardiovascular Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou 450046, China.

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Mishra S, Shelke V, Dagar N, Lech M, Gaikwad AB. Immunosuppressants against acute kidney injury: what to prefer or to avoid? Immunopharmacol Immunotoxicol 2024;46:341-354. [PMID: 38477877 DOI: 10.1080/08923973.2024.2330641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Accepted: 03/09/2024] [Indexed: 03/14/2024]

Gork I, Xiong F, Kitchlu A. Cancer drugs and acute kidney injury: new therapies and new challenges. Curr Opin Nephrol Hypertens 2024:00041552-990000000-00164. [PMID: 38712677 DOI: 10.1097/mnh.0000000000001001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/08/2024]

Selamet U, Ahdoot RS, Salasnek R, Abdelnour L, Hanna RM. Onconephrology: mitigation of renal injury in chemotherapy administration. Curr Opin Nephrol Hypertens 2024;33:257-266. [PMID: 38095483 DOI: 10.1097/mnh.0000000000000960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2024]

Zhou P, Gao Y, Kong Z, Wang J, Si S, Han W, Li J, Lv Z, Wang R. Immune checkpoint inhibitors and acute kidney injury. Front Immunol 2024;15:1353339. [PMID: 38464524 PMCID: PMC10920224 DOI: 10.3389/fimmu.2024.1353339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Accepted: 02/12/2024] [Indexed: 03/12/2024] Open

Moturi K, Sharma H, Hashemi-Sadraei N. Nephrotoxicity in the Age of Immune Checkpoint Inhibitors: Mechanisms, Diagnosis, and Management. Int J Mol Sci 2023;25:414. [PMID: 38203586 PMCID: PMC10778678 DOI: 10.3390/ijms25010414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 12/15/2023] [Accepted: 12/20/2023] [Indexed: 01/12/2024] Open

Gunay G, Maier KN, Hamsici S, Carvalho F, Timog TA, Acar H. Peptide aggregation-induced immunogenic cell death in a breast cancer spheroid model. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.10.31.565012. [PMID: 37961293 PMCID: PMC10635027 DOI: 10.1101/2023.10.31.565012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2023]

Parvathareddy V, Selamet U, Sen AA, Mamlouk O, Song J, Page VD, Abdelrahim M, Diab A, Abdel-Wahab N, Abudayyeh A. Infliximab for Treatment of Immune Adverse Events and Its Impact on Tumor Response. Cancers (Basel) 2023;15:5181. [PMID: 37958355 PMCID: PMC10649345 DOI: 10.3390/cancers15215181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 10/23/2023] [Accepted: 10/25/2023] [Indexed: 11/15/2023] Open

Abstract

Background: Immune-related adverse events (irAEs) challenge the use of immune checkpoint inhibitors (ICIs). We performed a retrospective study to evaluate response to infliximab for immune-related adverse event management, and infliximab's effect on progression-free survival (PFS) and overall survival (OS) with a focus on melanoma and genitourinary cancers. Methods: We retrospectively reviewed records of all cancer patients exposed to infliximab after immune checkpoint inhibitor (ICI) treatment from 2004 to 2021 at the MD Anderson Cancer Center. Survival was assessed utilizing the Kaplan-Meier method. Univariate and multivariate logistic regression was utilized to evaluate predictors of infliximab response, OS, and PFS. Results: We identified 185 cancer patients (93 melanoma and 37 genitourinary cancers) treated with ICI and who received infliximab to treat irAEs. Within 3 months of treatment initiation, 71% of the patients responded to infliximab, 27% had no response, and 2% had unknown response. Among different irAEs, colitis was associated with increased response to infliximab at 3 months, irrespective of the type of malignancy. We evaluated best tumor response before and after infliximab in the entire cohort and again in the melanoma and genitourinary (GU); the findings were similar in the melanoma cohort and the entire cohort, where best tumor response before and after infliximab was not significantly different. In the melanoma cohort, acute kidney injury (AKI) was associated with increased risk of death, p = 0.0109, and having response to infliximab was associated with decreased risk of death, p = 0.0383. Interestingly in GU cancer patients, myositis was associated with increased risk of death, p = 0.0041, and having a response to infliximab was marginally associated with decreased risk of death, p = 0.0992. As regards PFS, in a multivariate Cox regression model, having a history of cardiovascular disease remained significantly associated with shorter PFS in the melanoma cohort. For patients with GU cancers, response to infliximab was associated with longer PFS. Conclusions: Our study is among the largest retrospective analyses of infliximab use for irAE management. Patients with colitis were the best responders to infliximab. AKI before initiation of infliximab in the melanoma subcohort and myositis in GU subcohort are associated with higher risk of death. Our results indicate no association between infliximab and cancer progression with the exception of genitourinary cancers.

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Curkovic NB, Johnson DB. Updates in toxicities associated with immune checkpoint inhibitors. Expert Rev Clin Immunol 2023;19:1117-1129. [PMID: 37276071 PMCID: PMC10527235 DOI: 10.1080/1744666x.2023.2221434] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Accepted: 05/31/2023] [Indexed: 06/07/2023]

Fa'ak F, Buni M, Falohun A, Lu H, Song J, Johnson DH, Zobniw CM, Trinh VA, Awiwi MO, Tahon NH, Elsayes KM, Ludford K, Montazari EJ, Chernis J, Dimitrova M, Sandigursky S, Sparks JA, Abu-Shawer O, Rahma O, Thanarajasingam U, Zeman AM, Talukder R, Singh N, Chung SH, Grivas P, Daher M, Abudayyeh A, Osman I, Weber J, Tayar JH, Suarez-Almazor ME, Abdel-Wahab N, Diab A. Selective immune suppression using interleukin-6 receptor inhibitors for management of immune-related adverse events. J Immunother Cancer 2023;11:e006814. [PMID: 37328287 PMCID: PMC10277540 DOI: 10.1136/jitc-2023-006814] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/07/2023] [Indexed: 06/18/2023] Open

Abstract

BACKGROUND

Management of immune-related adverse events (irAEs) is important as they cause treatment interruption or discontinuation, more often seen with combination immune checkpoint inhibitor (ICI) therapy. Here, we retrospectively evaluated the safety and effectiveness of anti-interleukin-6 receptor (anti-IL-6R) as therapy for irAEs.

METHODS

We performed a retrospective multicenter study evaluating patients diagnosed with de novo irAEs or flare of pre-existing autoimmune disease following ICI and were treated with anti-IL-6R. Our objectives were to assess the improvement of irAEs as well as the overall tumor response rate (ORR) before and after anti-IL-6R treatment.

RESULTS

We identified a total of 92 patients who received therapeutic anti-IL-6R antibodies (tocilizumab or sarilumab). Median age was 61 years, 63% were men, 69% received anti-programmed cell death protein-1 (PD-1) antibodies alone, and 26% patients were treated with the combination of anti-cytotoxic T lymphocyte antigen-4 and anti-PD-1 antibodies. Cancer types were primarily melanoma (46%), genitourinary cancer (35%), and lung cancer (8%). Indications for using anti-IL-6R antibodies included inflammatory arthritis (73%), hepatitis/cholangitis (7%), myositis/myocarditis/myasthenia gravis (5%), polymyalgia rheumatica (4%), and one patient each with autoimmune scleroderma, nephritis, colitis, pneumonitis and central nervous system vasculitis. Notably, 88% of patients had received corticosteroids, and 36% received other disease-modifying antirheumatic drugs (DMARDs) as first-line therapies, but without adequate improvement. After initiation of anti-IL-6R (as first-line or post-corticosteroids and DMARDs), 73% of patients showed resolution or change to ≤grade 1 of irAEs after a median of 2.0 months from initiation of anti-IL-6R therapy. Six patients (7%) stopped anti-IL-6R due to adverse events. Of 70 evaluable patients by RECIST (Response Evaluation Criteria in Solid Tumors) V.1.1 criteria; the ORR was 66% prior versus 66% after anti-IL-6R (95% CI, 54% to 77%), with 8% higher complete response rate. Of 34 evaluable patients with melanoma, the ORR was 56% prior and increased to 68% after anti-IL-6R (p=0.04).

CONCLUSION

Targeting IL-6R could be an effective approach to treat several irAE types without hindering antitumor immunity. This study supports ongoing clinical trials evaluating the safety and efficacy of tocilizumab (anti-IL-6R antibody) in combination with ICIs (NCT04940299, NCT03999749).

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Affiliation(s)

Faisal Fa'ak Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York, USA
Maryam Buni University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Adewunmi Falohun University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Huifang Lu University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Juhee Song University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Daniel H Johnson Ochsner Health, New Orleans, Louisiana, USA
Chrystia M Zobniw University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Van A Trinh University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Muhammad Osama Awiwi University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Nourel Hoda Tahon University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Khaled M Elsayes University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Kaysia Ludford University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Emma J Montazari University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Julia Chernis University of Texas Health Science Center at Houston John P and Katherine G McGovern Medical School, Houston, Texas, USA
Maya Dimitrova Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York, USA
Sabina Sandigursky Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York, USA
Jeffrey A Sparks Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
Osama Abu-Shawer Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
Osama Rahma Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
Uma Thanarajasingam Mayo Clinic, Rochester, Minnesota, USA
Ashley M Zeman Mayo Clinic, Rochester, Minnesota, USA
Rafee Talukder Fred Hutchinson Cancer Center, University of Washington School of Medicine, Seattle, Washington, USA
Namrata Singh Fred Hutchinson Cancer Center, University of Washington School of Medicine, Seattle, Washington, USA
Sarah H Chung Fred Hutchinson Cancer Center, University of Washington School of Medicine, Seattle, Washington, USA
Petros Grivas Fred Hutchinson Cancer Center, University of Washington School of Medicine, Seattle, Washington, USA
May Daher University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Ala Abudayyeh University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Iman Osman Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York, USA
Jeffrey Weber Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York, USA
Jean H Tayar University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Maria E Suarez-Almazor University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Noha Abdel-Wahab University of Texas MD Anderson Cancer Center, Houston, Texas, USA Assiut University Faculty of Medicine, Assiut University Hospitals, Assiut, Egypt
Adi Diab University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Mamlouk O, Danesh FR. Immune Checkpoint Inhibitor-Associated Nephrotoxicity. Nephron Clin Pract 2023;148:11-15. [PMID: 37257429 DOI: 10.1159/000531297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Accepted: 05/23/2023] [Indexed: 06/02/2023] Open

Vitale I, Pietrocola F, Guilbaud E, Aaronson SA, Abrams JM, Adam D, Agostini M, Agostinis P, Alnemri ES, Altucci L, Amelio I, Andrews DW, Aqeilan RI, Arama E, Baehrecke EH, Balachandran S, Bano D, Barlev NA, Bartek J, Bazan NG, Becker C, Bernassola F, Bertrand MJM, Bianchi ME, Blagosklonny MV, Blander JM, Blandino G, Blomgren K, Borner C, Bortner CD, Bove P, Boya P, Brenner C, Broz P, Brunner T, Damgaard RB, Calin GA, Campanella M, Candi E, Carbone M, Carmona-Gutierrez D, Cecconi F, Chan FKM, Chen GQ, Chen Q, Chen YH, Cheng EH, Chipuk JE, Cidlowski JA, Ciechanover A, Ciliberto G, Conrad M, Cubillos-Ruiz JR, Czabotar PE, D'Angiolella V, Daugaard M, Dawson TM, Dawson VL, De Maria R, De Strooper B, Debatin KM, Deberardinis RJ, Degterev A, Del Sal G, Deshmukh M, Di Virgilio F, Diederich M, Dixon SJ, Dynlacht BD, El-Deiry WS, Elrod JW, Engeland K, Fimia GM, Galassi C, Ganini C, Garcia-Saez AJ, Garg AD, Garrido C, Gavathiotis E, Gerlic M, Ghosh S, Green DR, Greene LA, Gronemeyer H, Häcker G, Hajnóczky G, Hardwick JM, Haupt Y, He S, Heery DM, Hengartner MO, Hetz C, Hildeman DA, Ichijo H, Inoue S, Jäättelä M, Janic A, Joseph B, Jost PJ, Kanneganti TD, Karin M, Kashkar H, Kaufmann T, Kelly GL, Kepp O, Kimchi A, Kitsis RN, Klionsky DJ, Kluck R, Krysko DV, Kulms D, Kumar S, Lavandero S, Lavrik IN, Lemasters JJ, Liccardi G, Linkermann A, Lipton SA, Lockshin RA, López-Otín C, Luedde T, MacFarlane M, Madeo F, Malorni W, Manic G, Mantovani R, Marchi S, Marine JC, Martin SJ, Martinou JC, Mastroberardino PG, Medema JP, Mehlen P, Meier P, Melino G, Melino S, Miao EA, Moll UM, Muñoz-Pinedo C, Murphy DJ, Niklison-Chirou MV, Novelli F, Núñez G, Oberst A, Ofengeim D, Opferman JT, Oren M, Pagano M, Panaretakis T, Pasparakis M, Penninger JM, Pentimalli F, Pereira DM, Pervaiz S, Peter ME, Pinton P, Porta G, Prehn JHM, Puthalakath H, Rabinovich GA, Rajalingam K, Ravichandran KS, Rehm M, Ricci JE, Rizzuto R, Robinson N, Rodrigues CMP, Rotblat B, Rothlin CV, Rubinsztein DC, Rudel T, Rufini A, Ryan KM, Sarosiek KA, Sawa A, Sayan E, Schroder K, Scorrano L, Sesti F, Shao F, Shi Y, Sica GS, Silke J, Simon HU, Sistigu A, Stephanou A, Stockwell BR, Strapazzon F, Strasser A, Sun L, Sun E, Sun Q, Szabadkai G, Tait SWG, Tang D, Tavernarakis N, Troy CM, Turk B, Urbano N, Vandenabeele P, Vanden Berghe T, Vander Heiden MG, Vanderluit JL, Verkhratsky A, Villunger A, von Karstedt S, Voss AK, Vousden KH, Vucic D, Vuri D, Wagner EF, Walczak H, Wallach D, Wang R, Wang Y, Weber A, Wood W, Yamazaki T, Yang HT, Zakeri Z, Zawacka-Pankau JE, Zhang L, Zhang H, Zhivotovsky B, Zhou W, Piacentini M, Kroemer G, Galluzzi L. Apoptotic cell death in disease-Current understanding of the NCCD 2023. Cell Death Differ 2023;30:1097-1154. [PMID: 37100955 PMCID: PMC10130819 DOI: 10.1038/s41418-023-01153-w] [Citation(s) in RCA: 139] [Impact Index Per Article: 69.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 03/10/2023] [Accepted: 03/17/2023] [Indexed: 04/28/2023] Open

Affiliation(s)

Ilio Vitale IIGM - Italian Institute for Genomic Medicine, c/o IRCSS Candiolo, Torino, Italy. Candiolo Cancer Institute, FPO -IRCCS, Candiolo, Italy.
Federico Pietrocola Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden
Emma Guilbaud Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA
Stuart A Aaronson Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
John M Abrams Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA
Dieter Adam Institut für Immunologie, Kiel University, Kiel, Germany
Massimiliano Agostini Department of Experimental Medicine, University of Rome Tor Vergata, TOR, Rome, Italy
Patrizia Agostinis Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium VIB Center for Cancer Biology, Leuven, Belgium
Emad S Alnemri Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA, USA
Lucia Altucci Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy BIOGEM, Avellino, Italy
Ivano Amelio Division of Systems Toxicology, Department of Biology, University of Konstanz, Konstanz, Germany
David W Andrews Sunnybrook Research Institute, Toronto, ON, Canada Departments of Biochemistry and Medical Biophysics, University of Toronto, Toronto, ON, Canada
Rami I Aqeilan Hebrew University of Jerusalem, Lautenberg Center for Immunology & Cancer Research, Institute for Medical Research Israel-Canada (IMRIC), Faculty of Medicine, Jerusalem, Israel
Eli Arama Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
Eric H Baehrecke Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA
Siddharth Balachandran Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA, USA
Daniele Bano Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany
Nickolai A Barlev Department of Biomedicine, Nazarbayev University School of Medicine, Astana, Kazakhstan
Jiri Bartek Department of Medical Biochemistry and Biophysics, Science for Life Laboratory, Karolinska Institute, Stockholm, Sweden Danish Cancer Society Research Center, Copenhagen, Denmark
Nicolas G Bazan Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA, USA
Christoph Becker Department of Medicine 1, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany
Francesca Bernassola Department of Experimental Medicine, University of Rome Tor Vergata, TOR, Rome, Italy
Mathieu J M Bertrand VIB-UGent Center for Inflammation Research, Ghent, Belgium Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
Marco E Bianchi Università Vita-Salute San Raffaele, School of Medicine, Milan, Italy and Ospedale San Raffaele IRCSS, Milan, Italy
Mikhail V Blagosklonny Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
J Magarian Blander Department of Medicine, Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY, USA Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA Sandra and Edward Meyer Cancer Center, New York, NY, USA
Giovanni Blandino IRCSS Regina Elena National Cancer Institute, Rome, Italy
Klas Blomgren Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden Pediatric Hematology and Oncology, Karolinska University Hospital, Stockholm, Sweden
Christoph Borner Institute of Molecular Medicine and Cell Research, Medical Faculty, Albert Ludwigs University of Freiburg, Freiburg, Germany
Carl D Bortner Signal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, Durham, NC, USA
Pierluigi Bove Department of Experimental Medicine, University of Rome Tor Vergata, TOR, Rome, Italy
Patricia Boya Centro de Investigaciones Biologicas Margarita Salas, CSIC, Madrid, Spain
Catherine Brenner Université Paris-Saclay, CNRS, Institut Gustave Roussy, Aspects métaboliques et systémiques de l'oncogénèse pour de nouvelles approches thérapeutiques, Villejuif, France
Petr Broz Department of Immunobiology, University of Lausanne, Epalinges, Vaud, Switzerland
Thomas Brunner Department of Biology, University of Konstanz, Konstanz, Germany
Rune Busk Damgaard Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark
George A Calin Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Michelangelo Campanella Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, London, UK UCL Consortium for Mitochondrial Research, London, UK Department of Biology, University of Rome Tor Vergata, Rome, Italy
Eleonora Candi Department of Experimental Medicine, University of Rome Tor Vergata, TOR, Rome, Italy
Michele Carbone Thoracic Oncology, University of Hawaii Cancer Center, Honolulu, HI, USA
Didac Carmona-Gutierrez Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria
Francesco Cecconi Cell Stress and Survival Unit, Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center, Copenhagen, Denmark Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy Università Cattolica del Sacro Cuore, Rome, Italy
Francis K-M Chan Department of Immunology, Duke University School of Medicine, Durham, NC, USA
Guo-Qiang Chen State Key Lab of Oncogene and its related gene, Ren-Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Quan Chen College of Life Sciences, Nankai University, Tianjin, China
Youhai H Chen Shenzhen Institute of Advanced Technology (SIAT), Shenzhen, Guangdong, China
Emily H Cheng Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Jerry E Chipuk Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
John A Cidlowski Signal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, Durham, NC, USA
Aaron Ciechanover The Technion-Integrated Cancer Center, The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
Gennaro Ciliberto IRCSS Regina Elena National Cancer Institute, Rome, Italy
Marcus Conrad Helmholtz Munich, Institute of Metabolism and Cell Death, Neuherberg, Germany
Juan R Cubillos-Ruiz Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA
Peter E Czabotar The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia
Vincenzo D'Angiolella Department of Oncology, University of Oxford, Oxford, UK
Mads Daugaard Department of Urologic Sciences, Vancouver Prostate Centre, Vancouver, BC, Canada
Ted M Dawson Institute for Cell Engineering and the Departments of Neurology, Neuroscience and Pharmacology & Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Valina L Dawson Institute for Cell Engineering and the Departments of Neurology, Neuroscience and Pharmacology & Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Ruggero De Maria Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy Università Cattolica del Sacro Cuore, Rome, Italy
Bart De Strooper VIB Centre for Brain & Disease Research, Leuven, Belgium Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium The Francis Crick Institute, London, UK UK Dementia Research Institute at UCL, University College London, London, UK
Klaus-Michael Debatin Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany
Ralph J Deberardinis Howard Hughes Medical Institute and Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA
Alexei Degterev Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA, USA
Giannino Del Sal Department of Life Sciences, University of Trieste, Trieste, Italy International Centre for Genetic Engineering and Biotechnology (ICGEB), Area Science Park-Padriciano, Trieste, Italy IFOM ETS, the AIRC Institute of Molecular Oncology, Milan, Italy
Mohanish Deshmukh Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC, USA
Francesco Di Virgilio Department of Medical Sciences, University of Ferrara, Ferrara, Italy
Marc Diederich College of Pharmacy, Seoul National University, Seoul, South Korea
Scott J Dixon Department of Biology, Stanford University, Stanford, CA, USA
Brian D Dynlacht Department of Pathology, New York University Cancer Institute, New York University School of Medicine, New York, NY, USA
Wafik S El-Deiry Division of Hematology/Oncology, Brown University and the Lifespan Cancer Institute, Providence, RI, USA Legorreta Cancer Center at Brown University, The Warren Alpert Medical School, Brown University, Providence, RI, USA Department of Pathology and Laboratory Medicine, The Warren Alpert Medical School, Brown University, Providence, RI, USA
John W Elrod Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
Kurt Engeland Molecular Oncology, University of Leipzig, Leipzig, Germany
Gian Maria Fimia Department of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases 'L. Spallanzani' IRCCS, Rome, Italy Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
Claudia Galassi Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA
Carlo Ganini Department of Experimental Medicine, University of Rome Tor Vergata, TOR, Rome, Italy Biochemistry Laboratory, Dermopatic Institute of Immaculate (IDI) IRCCS, Rome, Italy
Ana J Garcia-Saez CECAD, Institute of Genetics, University of Cologne, Cologne, Germany
Abhishek D Garg Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
Carmen Garrido INSERM, UMR, 1231, Dijon, France Faculty of Medicine, Université de Bourgogne Franche-Comté, Dijon, France Anti-cancer Center Georges-François Leclerc, Dijon, France
Evripidis Gavathiotis Department of Biochemistry, Albert Einstein College of Medicine, New York, NY, USA Department of Medicine, Albert Einstein College of Medicine, New York, NY, USA Albert Einstein Cancer Center, Albert Einstein College of Medicine, New York, NY, USA Institute for Aging Research, Albert Einstein College of Medicine, New York, NY, USA Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, New York, NY, USA
Motti Gerlic Department of Clinical Microbiology and Immunology, Sackler school of Medicine, Tel Aviv university, Tel Aviv, Israel
Sourav Ghosh Department of Neurology and Department of Pharmacology, Yale School of Medicine, New Haven, CT, USA
Douglas R Green Department of Immunology, St Jude Children's Research Hospital, Memphis, TN, USA
Lloyd A Greene Department of Pathology and Cell Biology, Columbia University, New York, NY, USA
Hinrich Gronemeyer Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France Centre National de la Recherche Scientifique, UMR7104, Illkirch, France Institut National de la Santé et de la Recherche Médicale, U1258, Illkirch, France Université de Strasbourg, Illkirch, France
Georg Häcker Faculty of Medicine, Institute of Medical Microbiology and Hygiene, Medical Center, University of Freiburg, Freiburg, Germany BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany
György Hajnóczky MitoCare Center, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
J Marie Hardwick Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA Departments of Molecular Microbiology and Immunology, Pharmacology, Oncology and Neurology, Johns Hopkins Bloomberg School of Public Health and School of Medicine, Baltimore, MD, USA
Ygal Haupt VITTAIL Ltd, Melbourne, VIC, Australia Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
Sudan He Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China Suzhou Institute of Systems Medicine, Suzhou, Jiangsu, China
David M Heery School of Pharmacy, University of Nottingham, Nottingham, UK
Michael O Hengartner ETH Board, Zurich, Switzerland
Claudio Hetz Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile Center for Geroscience, Brain Health and Metabolism, Santiago, Chile Center for Molecular Studies of the Cell, Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile Buck Institute for Research on Aging, Novato, CA, USA
David A Hildeman Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
Hidenori Ichijo Laboratory of Cell Signaling, The University of Tokyo, Tokyo, Japan
Satoshi Inoue National Cancer Center Research Institute, Tokyo, Japan
Marja Jäättelä Cell Death and Metabolism, Center for Autophagy, Recycling and Disease, Danish Cancer Society Research Center, Copenhagen, Denmark Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark
Ana Janic Department of Medicine and Life Sciences, Pompeu Fabra University, Barcelona, Spain
Bertrand Joseph Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
Philipp J Jost Clinical Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
Thirumala-Devi Kanneganti Department of Immunology, St Jude Children's Research Hospital, Memphis, TN, USA
Michael Karin Departments of Pharmacology and Pathology, School of Medicine, University of California San Diego, San Diego, CA, USA
Hamid Kashkar CECAD Research Center, Institute for Molecular Immunology, University of Cologne, Cologne, Germany
Thomas Kaufmann Institute of Pharmacology, University of Bern, Bern, Switzerland
Gemma L Kelly The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia
Oliver Kepp Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Center, Université Paris Saclay, Villejuif, France Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France
Adi Kimchi Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
Richard N Kitsis Department of Biochemistry, Albert Einstein College of Medicine, New York, NY, USA Department of Medicine, Albert Einstein College of Medicine, New York, NY, USA Albert Einstein Cancer Center, Albert Einstein College of Medicine, New York, NY, USA Institute for Aging Research, Albert Einstein College of Medicine, New York, NY, USA Department of Cell Biology, Albert Einstein College of Medicine, New York, NY, USA Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, New York, NY, USA
Daniel J Klionsky Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA
Ruth Kluck The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia
Dmitri V Krysko Cell Death Investigation and Therapy Lab, Department of Human Structure and Repair, Ghent University, Ghent, Belgium Cancer Research Institute Ghent (CRIG), Ghent, Belgium
Dagmar Kulms Department of Dermatology, Experimental Dermatology, TU-Dresden, Dresden, Germany National Center for Tumor Diseases Dresden, TU-Dresden, Dresden, Germany
Sharad Kumar Centre for Cancer Biology, University of South Australia, Adelaide, SA, Australia Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA, Australia
Sergio Lavandero Universidad de Chile, Facultad Ciencias Quimicas y Farmaceuticas & Facultad Medicina, Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile Department of Internal Medicine, Cardiology Division, University of Texas Southwestern Medical Center, Dallas, TX, USA
Inna N Lavrik Translational Inflammation Research, Medical Faculty, Otto von Guericke University, Magdeburg, Germany
John J Lemasters Departments of Drug Discovery & Biomedical Sciences and Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, SC, USA
Gianmaria Liccardi Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany
Andreas Linkermann Division of Nephrology, Department of Internal Medicine 3, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany Biotechnology Center, Technische Universität Dresden, Dresden, Germany
Stuart A Lipton Neurodegeneration New Medicines Center and Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA Department of Neurosciences, University of California, San Diego, School of Medicine, La Jolla, CA, USA Department of Neurology, Yale School of Medicine, New Haven, CT, USA
Richard A Lockshin Department of Biology, Queens College of the City University of New York, Flushing, NY, USA St. John's University, Jamaica, NY, USA
Carlos López-Otín Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología (IUOPA), Universidad de Oviedo, Oviedo, Spain
Tom Luedde Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Duesseldorf, Heinrich Heine University, Duesseldorf, Germany
Marion MacFarlane Medical Research Council Toxicology Unit, University of Cambridge, Cambridge, UK
Frank Madeo Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria BioTechMed Graz, Graz, Austria Field of Excellence BioHealth - University of Graz, Graz, Austria
Walter Malorni Center for Global Health, Università Cattolica del Sacro Cuore, Rome, Italy
Gwenola Manic IIGM - Italian Institute for Genomic Medicine, c/o IRCSS Candiolo, Torino, Italy Candiolo Cancer Institute, FPO -IRCCS, Candiolo, Italy
Roberto Mantovani Dipartimento di Bioscienze, Università degli Studi di Milano, Milano, Italy
Saverio Marchi Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona, Italy
Jean-Christophe Marine VIB Center for Cancer Biology, Leuven, Belgium Department of Oncology, KU Leuven, Leuven, Belgium
Seamus J Martin Department of Genetics, Trinity College, Dublin, 2, Ireland
Jean-Claude Martinou Department of Cell Biology, Faculty of Sciences, University of Geneva, Geneva, Switzerland
Pier G Mastroberardino Department of Molecular Genetics, Rotterdam, the Netherlands IFOM-ETS The AIRC Institute for Molecular Oncology, Milan, Italy Department of Life, Health, and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
Jan Paul Medema Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands Oncode Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Patrick Mehlen Apoptosis, Cancer, and Development Laboratory, Equipe labellisée 'La Ligue', LabEx DEVweCAN, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Centre Léon Bérard, Université de Lyon, Université Claude Bernard Lyon1, Lyon, France
Pascal Meier The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK
Gerry Melino Department of Experimental Medicine, University of Rome Tor Vergata, TOR, Rome, Italy
Sonia Melino Department of Chemical Science and Technologies, University of Rome Tor Vergata, Rome, Italy
Edward A Miao Department of Immunology, Duke University School of Medicine, Durham, NC, USA
Ute M Moll Department of Pathology and Stony Brook Cancer Center, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA
Cristina Muñoz-Pinedo Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Spain
Daniel J Murphy School of Cancer Sciences, University of Glasgow, Glasgow, UK Cancer Research UK Beatson Institute, Glasgow, UK
Maria Victoria Niklison-Chirou Department of Pharmacy & Pharmacology, Centre for Therapeutic Innovation, University of Bath, Bath, UK
Flavia Novelli Thoracic Oncology, University of Hawaii Cancer Center, Honolulu, HI, USA
Gabriel Núñez Department of Pathology and Rogel Cancer Center, The University of Michigan, Ann Arbor, MI, USA
Andrew Oberst Department of Immunology, University of Washington, Seattle, WA, USA
Dimitry Ofengeim Rare and Neuroscience Therapeutic Area, Sanofi, Cambridge, MA, USA
Joseph T Opferman Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA
Moshe Oren Department of Molecular Cell Biology, The Weizmann Institute, Rehovot, Israel
Michele Pagano Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine and Howard Hughes Medical Institute, New York, NY, USA
Theocharis Panaretakis Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden Department of GU Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA
Manolis Pasparakis CECAD, Institute of Genetics, University of Cologne, Cologne, Germany
Josef M Penninger IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, Canada
Francesca Pentimalli Department of Medicine and Surgery, LUM University, Casamassima, Bari, Italy
David M Pereira REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal
Shazib Pervaiz Department of Physiology, YLL School of Medicine, National University of Singapore, Singapore, Singapore NUS Centre for Cancer Research (N2CR), National University of Singapore, Singapore, Singapore National University Cancer Institute, NUHS, Singapore, Singapore ISEP, NUS Graduate School, National University of Singapore, Singapore, Singapore
Marcus E Peter Department of Medicine, Division Hematology/Oncology, Northwestern University, Chicago, IL, USA
Paolo Pinton Department of Medical Sciences, University of Ferrara, Ferrara, Italy
Giovanni Porta Center of Genomic Medicine, Department of Medicine and Surgery, University of Insubria, Varese, Italy
Jochen H M Prehn Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland (RCSI) University of Medicine and Health Sciences, Dublin 2, Ireland
Hamsa Puthalakath Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, Australia
Gabriel A Rabinovich Laboratorio de Glicomedicina. Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
Krishnaraj Rajalingam Cell Biology Unit, University Medical Center Mainz, Mainz, Germany
Kodi S Ravichandran VIB-UGent Center for Inflammation Research, Ghent, Belgium Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA Center for Cell Clearance, Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA
Markus Rehm Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany
Jean-Ehrland Ricci Université Côte d'Azur, INSERM, C3M, Equipe labellisée Ligue Contre le Cancer, Nice, France
Rosario Rizzuto Department of Biomedical Sciences, University of Padua, Padua, Italy
Nirmal Robinson Centre for Cancer Biology, University of South Australia, Adelaide, SA, Australia
Cecilia M P Rodrigues Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
Barak Rotblat Department of Life sciences, Ben Gurion University of the Negev, Beer Sheva, Israel The NIBN, Beer Sheva, Israel
Carla V Rothlin Department of Immunobiology and Department of Pharmacology, Yale School of Medicine, New Haven, CT, USA
David C Rubinsztein Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge, UK UK Dementia Research Institute, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, UK
Thomas Rudel Microbiology Biocentre, University of Würzburg, Würzburg, Germany
Alessandro Rufini Dipartimento di Bioscienze, Università degli Studi di Milano, Milano, Italy University of Leicester, Leicester Cancer Research Centre, Leicester, UK
Kevin M Ryan School of Cancer Sciences, University of Glasgow, Glasgow, UK Cancer Research UK Beatson Institute, Glasgow, UK
Kristopher A Sarosiek John B. Little Center for Radiation Sciences, Harvard School of Public Health, Boston, MA, USA Department of Systems Biology, Lab of Systems Pharmacology, Harvard Program in Therapeutics Science, Harvard Medical School, Boston, MA, USA Department of Environmental Health, Molecular and Integrative Physiological Sciences Program, Harvard School of Public Health, Boston, MA, USA
Akira Sawa Johns Hopkins Schizophrenia Center, Johns Hopkins University, Baltimore, MD, USA
Emre Sayan Faculty of Medicine, Cancer Sciences Unit, University of Southampton, Southampton, UK
Kate Schroder Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, Australia
Luca Scorrano Department of Biology, University of Padua, Padua, Italy Veneto Institute of Molecular Medicine, Padua, Italy
Federico Sesti Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Rutgers University, NJ, USA
Feng Shao National Institute of Biological Sciences, Beijing, PR China
Yufang Shi Department of Experimental Medicine, University of Rome Tor Vergata, TOR, Rome, Italy The Third Affiliated Hospital of Soochow University and State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University, Suzhou, Jiangsu, China CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China
Giuseppe S Sica Department of Surgical Science, University Tor Vergata, Rome, Italy
John Silke The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia
Hans-Uwe Simon Institute of Pharmacology, University of Bern, Bern, Switzerland Institute of Biochemistry, Brandenburg Medical School, Neuruppin, Germany
Antonella Sistigu Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
Anastasis Stephanou European University Cyprus, School of Medicine, Nicosia, Cyprus
Brent R Stockwell Department of Biological Sciences and Department of Chemistry, Columbia University, New York, NY, USA
Flavie Strapazzon IRCCS Fondazione Santa Lucia, Rome, Italy Univ Lyon, Univ Lyon 1, Physiopathologie et Génétique du Neurone et du Muscle, UMR5261, U1315, Institut NeuroMyogène CNRS, INSERM, Lyon, France
Andreas Strasser The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia
Liming Sun State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China
Erwei Sun Department of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China
Qiang Sun Laboratory of Cell Engineering, Institute of Biotechnology, Beijing, China Research Unit of Cell Death Mechanism, 2021RU008, Chinese Academy of Medical Science, Beijing, China
Gyorgy Szabadkai Department of Biomedical Sciences, University of Padua, Padua, Italy Department of Cell and Developmental Biology, Consortium for Mitochondrial Research, University College London, London, UK
Stephen W G Tait School of Cancer Sciences, University of Glasgow, Glasgow, UK Cancer Research UK Beatson Institute, Glasgow, UK
Daolin Tang Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
Nektarios Tavernarakis Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Crete, Greece Department of Basic Sciences, School of Medicine, University of Crete, Heraklion, Crete, Greece
Carol M Troy Departments of Pathology & Cell Biology and Neurology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA
Boris Turk Department of Biochemistry and Molecular and Structural Biology, J. Stefan Institute, Ljubljana, Slovenia Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia
Nicoletta Urbano Department of Oncohaematology, University of Rome Tor Vergata, TOR, Rome, Italy
Peter Vandenabeele VIB-UGent Center for Inflammation Research, Ghent, Belgium Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium Methusalem Program, Ghent University, Ghent, Belgium
Tom Vanden Berghe VIB-UGent Center for Inflammation Research, Ghent, Belgium Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium Infla-Med Centre of Excellence, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
Matthew G Vander Heiden Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA Dana-Farber Cancer Institute, Boston, MA, USA
Jacqueline L Vanderluit Division of BioMedical Sciences, Memorial University, St. John's, NL, Canada
Alexei Verkhratsky Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK Achucarro Center for Neuroscience, IKERBASQUE, Bilbao, Spain School of Forensic Medicine, China Medical University, Shenyang, China State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania
Andreas Villunger Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria The Research Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences (OeAW), Vienna, Austria The Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases (LBI-RUD), Vienna, Austria
Silvia von Karstedt Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, Cologne, Germany CECAD Cluster of Excellence, University of Cologne, Cologne, Germany Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, Cologne, Germany
Anne K Voss The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia
Karen H Vousden The Francis Crick Institute, London, UK
Domagoj Vucic Department of Early Discovery Biochemistry, Genentech, South San Francisco, CA, USA
Daniela Vuri Department of Experimental Medicine, University of Rome Tor Vergata, TOR, Rome, Italy
Erwin F Wagner Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria Department of Dermatology, Medical University of Vienna, Vienna, Austria
Henning Walczak Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany CECAD Cluster of Excellence, University of Cologne, Cologne, Germany Centre for Cell Death, Cancer and Inflammation, UCL Cancer Institute, University College London, London, UK
David Wallach Department of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot, Israel
Ruoning Wang Center for Childhood Cancer and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA
Ying Wang Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China
Achim Weber University of Zurich and University Hospital Zurich, Department of Pathology and Molecular Pathology, Zurich, Switzerland University of Zurich, Institute of Molecular Cancer Research, Zurich, Switzerland
Will Wood Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
Takahiro Yamazaki Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA
Huang-Tian Yang Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China
Zahra Zakeri Queens College and Graduate Center, City University of New York, Flushing, NY, USA
Joanna E Zawacka-Pankau Department of Medicine Huddinge, Karolinska Institute, Stockholm, Sweden Department of Biochemistry, Laboratory of Biophysics and p53 protein biology, Medical University of Warsaw, Warsaw, Poland
Lin Zhang Department of Pharmacology & Chemical Biology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Haibing Zhang CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China
Boris Zhivotovsky Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russia
Wenzhao Zhou Laboratory of Cell Engineering, Institute of Biotechnology, Beijing, China Research Unit of Cell Death Mechanism, 2021RU008, Chinese Academy of Medical Science, Beijing, China
Mauro Piacentini Department of Biology, University of Rome Tor Vergata, Rome, Italy National Institute for Infectious Diseases IRCCS "Lazzaro Spallanzani", Rome, Italy
Guido Kroemer Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Center, Université Paris Saclay, Villejuif, France Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France Institut du Cancer Paris CARPEM, Department of Biology, Hôpital Européen Georges Pompidou, AP-HP, Paris, France
Lorenzo Galluzzi Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA. Sandra and Edward Meyer Cancer Center, New York, NY, USA. Caryl and Israel Englander Institute for Precision Medicine, New York, NY, USA.

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Seethapathy H, Herrmann SM, Rashidi A. Immune Checkpoint Inhibitor-Associated AKI: Debates in Diagnosis, Management, and Rechallenge. Semin Nephrol 2023;42:151346. [PMID: 37137187 DOI: 10.1016/j.semnephrol.2023.151346] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/05/2023]

Farooqui N, Zaidi M, Vaughan L, McKee TD, Ahsan E, Pavelko KD, Villasboas JC, Markovic S, Taner T, Leung N, Dong H, Alexander MP, Herrmann SM. Cytokines and Immune Cell Phenotype in Acute Kidney Injury Associated With Immune Checkpoint Inhibitors. Kidney Int Rep 2023;8:628-641. [PMID: 36938084 PMCID: PMC10014345 DOI: 10.1016/j.ekir.2022.11.020] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 10/25/2022] [Accepted: 11/28/2022] [Indexed: 12/12/2022] Open

Abstract

Introduction

Immune checkpoint inhibitors (ICIs) induce impressive antitumor responses but may lead to acute kidney injury (AKI) associated with ICI therapy (AKI-ICI). Biomarkers distinguishing AKI-ICI from AKI because of other causes (AKI-other) are currently lacking. Because ICIs block immunoregulatory pathways, we hypothesized that biomarkers related to immune cell dysregulation, including tumor necrosis factor alpha (TNF-α) and other markers of B and T cell activation in the systemic circulation and kidney tissue, may aid with the diagnosis of AKI-ICI.

Methods

This is a prospective study consisting of 24 participants who presented with AKI during ICI therapy, adjudicated to either have AKI-ICI (n = 14) or AKI-other (n = 10). We compared markers of kidney inflammation and injury (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1) as well as plasma and urine levels of T cell-associated cytokines (TNF-α, interferon-γ, interleukin (IL)-2, IL-4, IL-6, IL-8, IL-9, and IL-10) between groups. We also compared T-cell responses in the systemic circulation and in kidney tissue across groups, using mass cytometry systems.

Results

We observed increase in several specific immune cells, including CD4 memory, T helper cells, and dendritic cells in the kidney tissue, as well as in the urine cytokines IL-2, IL-10, and TNF-α, in patients who developed AKI-ICI compared to patients with AKI-other (P < 0.05 for all). The discriminatory ability of TNF-α on AKI cause was strong (area under the curve = 0.814, 95% confidence interval: 0.623-1.00. The CD4+ T cells with memory phenotype formed the dominant subset.

Conclusion

These results suggest that specific T-cell responses and their respective cytokines may be indicative of AKI associated with ICI therapy and may help to differentiate AKI-ICI from AKI-other. Urine TNF-α is a promising biomarker for AKI-ICI, which is most often caused by acute interstitial nephritis (AIN), and TNF-α pathway may serve as a potential target for therapeutic intervention.

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Haanen J, Obeid M, Spain L, Carbonnel F, Wang Y, Robert C, Lyon AR, Wick W, Kostine M, Peters S, Jordan K, Larkin J. Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2022;33:1217-1238. [PMID: 36270461 DOI: 10.1016/j.annonc.2022.10.001] [Citation(s) in RCA: 391] [Impact Index Per Article: 130.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 09/30/2022] [Accepted: 10/02/2022] [Indexed: 11/17/2022] Open

Pathologic Predictors of Response to Treatment of Immune Checkpoint Inhibitor–Induced Kidney Injury. Cancers (Basel) 2022;14:cancers14215267. [DOI: 10.3390/cancers14215267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 10/22/2022] [Accepted: 10/22/2022] [Indexed: 11/16/2022] Open

Abstract Background: Immune-related adverse events are a management challenge in patients receiving immune checkpoint inhibitors (ICIs). The most common renal immune-related adverse event, acute interstitial nephritis (AIN), is associated with patient morbidity and mortality. AIN, characterized by infiltration of renal tissue with immune cells, may be analogous to kidney transplant rejection. We evaluated clinical variables and pathologic findings to identify predictors of renal response and overall survival (OS) in patients with ICI-induced AIN. Design, setting, participants, and measurements: We reviewed the records and biopsy specimens of all 35 patients treated for ICI-induced AIN at our institution, between August 2007 and August 2020, who had biopsy specimens available. Two board-certified renal pathologists graded the severity of inflammation and chronicity using transplant rejection Banff criteria and performed immunohistochemistry analysis. Patients were categorized as renal responders if creatinine had any improvement or returned to baseline within 3 months of initiating treatment for AIN. Clinical and pathologic characteristics and OS were compared between responders and non-responders. Results: Patients with high levels of interstitial fibrosis were less likely to be responders than those with less fibrosis (p = 0.02). Inflammation, tubulitis, the number of eosinophils and neutrophils, and the clustering or presence of CD8+, CD4+, CD20+, or CD68+ cells were not associated with renal response. Responders had better OS than non-responders (12-month OS rate 77% compared with 27%, p = 0.025). Responders who received concurrent ICIs had the best OS, and non-responders who did not receive concurrent ICIs had the worst OS (12-month OS rate 100% for renal response and concurrent ICIs, 72% for renal response and no concurrent ICIs, and 27% for no renal response and no concurrent ICIs; p = 0.041). Conclusions: This is the first analysis of ICI induced nephritis where a detailed pathological and clinical evaluation was performed to predict renal response. Low levels of interstitial fibrosis in kidney tissue are associated with renal response to treatment for ICI-induced AIN, and the renal response and use of concurrent ICIs are associated with better OS in these patients. Our findings highlight the importance of the early diagnosis and treatment of ICI-AIN, while continuing concurrent ICI therapy. Collapse

Miao J, Sise ME, Herrmann SM. Immune checkpoint inhibitor related nephrotoxicity: Advances in clinicopathologic features, noninvasive approaches, and therapeutic strategy and rechallenge. FRONTIERS IN NEPHROLOGY 2022;2:1017921. [PMID: 37674988 PMCID: PMC10479679 DOI: 10.3389/fneph.2022.1017921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 09/28/2022] [Indexed: 09/08/2023]

Sprangers B, Leaf DE, Porta C, Soler MJ, Perazella MA. Diagnosis and management of immune checkpoint inhibitor-associated acute kidney injury. Nat Rev Nephrol 2022;18:794-805. [PMID: 36168055 DOI: 10.1038/s41581-022-00630-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/24/2022] [Indexed: 11/10/2022]

Immune checkpoint inhibitors and kidney disease. Curr Opin Nephrol Hypertens 2022;31:449-455. [PMID: 35894279 DOI: 10.1097/mnh.0000000000000805] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]

Shaikh A. Immunotherapies and Renal Injury. CURRENT OPINION IN TOXICOLOGY 2022;31:100362. [PMID: 39086475 PMCID: PMC11290437 DOI: 10.1016/j.cotox.2022.100362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]

Borówka M, Łącki-Zynzeling S, Nicze M, Kozak S, Chudek J. Adverse Renal Effects of Anticancer Immunotherapy: A Review. Cancers (Basel) 2022;14:4086. [PMID: 36077623 PMCID: PMC9454552 DOI: 10.3390/cancers14174086] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 08/18/2022] [Accepted: 08/22/2022] [Indexed: 11/17/2022] Open

Weng J, Ajani JA, Murphy MB, Badgwell BD, Tchakarov AS, Mamlouk O, Das P. Immunotherapy Recall: Chemoradiation-Induced Reactivation of Immune Checkpoint Inhibitor Nephritis. JCO Precis Oncol 2022;6:e2200049. [PMID: 35952321 DOI: 10.1200/po.22.00049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open

Chen C, Xie D, Gewirtz DA, Li N. Nephrotoxicity in cancer treatment: An update. Adv Cancer Res 2022;155:77-129. [PMID: 35779877 PMCID: PMC11017963 DOI: 10.1016/bs.acr.2022.03.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]

Perazella MA, Rosner MH. Drug-Induced Acute Kidney Injury. Clin J Am Soc Nephrol 2022;17:1220-1233. [PMID: 35273009 PMCID: PMC9435983 DOI: 10.2215/cjn.11290821] [Citation(s) in RCA: 122] [Impact Index Per Article: 40.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]

Abdelrahim M, Abudayyeh A. Renal Toxicity. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022;1342:389-397. [PMID: 34972976 DOI: 10.1007/978-3-030-79308-1_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]

Smithy JW, Faleck DM, Postow MA. Facts and Hopes in Prediction, Diagnosis, and Treatment of Immune-Related Adverse Events. Clin Cancer Res 2021;28:1250-1257. [PMID: 34921018 DOI: 10.1158/1078-0432.ccr-21-1240] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 10/20/2021] [Accepted: 12/07/2021] [Indexed: 11/16/2022]

Seethapathy H, Herrmann SM, Sise ME. Immune Checkpoint Inhibitors and Kidney Toxicity: Advances in Diagnosis and Management. Kidney Med 2021;3:1074-1081. [PMID: 34939017 PMCID: PMC8664750 DOI: 10.1016/j.xkme.2021.08.008] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open

Manohar S, Jhaveri KD, Perazella MA. Immunotherapy-Related Acute Kidney Injury. Adv Chronic Kidney Dis 2021;28:429-437.e1. [PMID: 35190109 DOI: 10.1053/j.ackd.2021.07.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 06/28/2021] [Accepted: 07/08/2021] [Indexed: 11/11/2022]

Gebauer E, Bechtel-Walz W, Schell C, Erbel M, Walz G, Hermle T. Development of Nivolumab/Ipilimumab-Associated Autoimmune Nephritis during Steroid Therapy. Case Rep Nephrol Dial 2021;11:270-274. [PMID: 34703826 PMCID: PMC8460889 DOI: 10.1159/000517502] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Accepted: 05/29/2021] [Indexed: 12/17/2022] Open