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Singvogel K, Schittek B. Dormancy of cutaneous melanoma. Cancer Cell Int 2024; 24:88. [PMID: 38419052 PMCID: PMC10903048 DOI: 10.1186/s12935-024-03278-5] [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: 10/09/2023] [Accepted: 02/19/2024] [Indexed: 03/02/2024] Open
Abstract
Many cancer-related deaths including melanoma result from metastases that develop months or years after the initial cancer therapy. Even the most effective drugs and immune therapies rarely eradicate all tumor cells. Instead, they strongly reduce cancer burden, permitting dormant cancer cells to persist in niches, where they establish a cellular homeostasis with their host without causing clinical symptoms. Dormant cancers respond poorly to most drugs and therapies since they do not proliferate and hide in niches. It therefore remains a major challenge to develop novel therapies for dormant cancers. In this review we focus on the mechanisms regulating the initiation of cutaneous melanoma dormancy as well as those which are involved in reawakening of dormant cutaneous melanoma cells. In recent years the role of neutrophils and niche components in reawakening of melanoma cells came into focus and indicate possible future therapeutic applications. Sophisticated in vitro and in vivo melanoma dormancy models are needed to make progress in this field and are discussed.
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Affiliation(s)
- Kathrin Singvogel
- Division of Dermatooncology, Department of Dermatology, University of Tübingen, Liebermeisterstr. 25, D -72076 , Tübingen, Germany
| | - Birgit Schittek
- Division of Dermatooncology, Department of Dermatology, University of Tübingen, Liebermeisterstr. 25, D -72076 , Tübingen, Germany.
- Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tübingen, Tübingen, Germany.
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2
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Abstract
T cells can acquire a broad spectrum of differentiation states following activation. At the extreme ends of this continuum are short-lived cells equipped with effector machinery and more quiescent, long-lived cells with heightened proliferative potential and stem cell-like developmental plasticity. The latter encompass stem-like exhausted T cells and memory T cells, both of which have recently emerged as key determinants of cancer immunity and response to immunotherapy. Here, we discuss key similarities and differences in the regulation and function of stem-like exhausted CD8+ T cells and memory CD8+ T cells, and consider their context-specific contributions to protective immunity in diverse outcomes of cancer, including tumour escape, long-term control and eradication. Finally, we emphasize how recent advances in the understanding of the molecular regulation of stem-like exhausted T cells and memory T cells are being explored for clinical benefit in cancer immunotherapies such as checkpoint inhibition, adoptive cell therapy and vaccination.
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Affiliation(s)
- Thomas Gebhardt
- Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia.
| | - Simone L Park
- Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Institute for Immunology and Immune Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Ian A Parish
- Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
- Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
- John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.
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3
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Rainey MA, Allen CT, Craveiro M. Egress of resident memory T cells from tissue with neoadjuvant immunotherapy: Implications for systemic anti-tumor immunity. Oral Oncol 2023; 146:106570. [PMID: 37738775 PMCID: PMC10591905 DOI: 10.1016/j.oraloncology.2023.106570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Revised: 09/11/2023] [Accepted: 09/16/2023] [Indexed: 09/24/2023]
Abstract
INTRODUCTION Resident memory T (TRM) cells are embedded in peripheral tissue and capable of acting as sentinels that can respond quickly to repeat pathogen exposure as part of an endogenous anti-microbial immune response. Recent evidence suggests that chronic antigen exposure and other microenvironment cues may promote the development of TRM cells within solid tumors as well, and that this TRM phenotype can sequester tumor-specific T cells into tumors and out of circulation resulting in limited systemic antitumor immunity. Here, we perform a review of the published English literature and describe tissue-specific mediators of TRM cell differentiation in states of infection and malignancy with special focus on the role of TGF-β and how targeting TGF-β signaling could be used as a therapeutical approach to promote tumor systemic immunity. DISCUSSION The presence of TRM cells with antigen specificity to neoepitopes in tumors associates with positive clinical prognosis and greater responsiveness to immunotherapy. Recent evidence indicates that solid tumors may act as reservoirs for tumor specific TRM cells and limit their circulation - possibly resulting in impaired systemic antitumor immunity. TRM cells utilize specific mechanisms to egress from peripheral tissues into circulation and other peripheral sites, and emerging evidence indicates that immunotherapeutic approaches may initiate these processes and increase systemic antitumor immunity. CONCLUSIONS Reversing tumor sequestration of tumor-specific T cells prior to surgical removal or radiation of tumor may increase systemic antitumor immunity. This finding may underlie the improved recurrence free survival observed with neoadjuvant immunotherapy in clinical trials.
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Affiliation(s)
- Magdalena A Rainey
- Head and Neck Section, Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Clint T Allen
- National Institutes of Health, 9000 Rockville Pike, Building 10, Room 7N240C, Bethesda, MD 20892, USA.
| | - Marco Craveiro
- Head and Neck Section, Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
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4
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Hoffmann JC, Schön MP. Integrin α E(CD103)β 7 in Epithelial Cancer. Cancers (Basel) 2021; 13:6211. [PMID: 34944831 PMCID: PMC8699740 DOI: 10.3390/cancers13246211] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/29/2021] [Accepted: 12/08/2021] [Indexed: 01/22/2023] Open
Abstract
Interactions of both the innate and the adaptive immune system with tumors are complex and often influence courses and therapeutic treatments in unanticipated ways. Based on the concept that CD8+T cells can mediate important antitumor effects, several therapies now aim to amplify their specific activity. A subpopulation of CD8+ tissue-resident T lymphocytes that express the αE(CD103)β7 integrin has raised particular interest. This receptor presumably contributes to the recruitment and retention of tumor-infiltrating immune cells through interaction with its ligand, E-cadherin. It appears to have regulatory functions and is thought to be a component of some immunological synapses. In TGF-rich environments, the αE(CD103)β7/E-cadherin-interaction enhances the binding strength between tumor cells and infiltrating T lymphocytes. This activity facilitates the release of lytic granule contents and cytokines as well as further immune responses and the killing of target cells. Expression of αE(CD103)β7 in some tumors is associated with a rather favorable prognosis, perhaps with the notable exception of squamous cell carcinoma of the skin. Although epithelial skin tumors are by far the most common tumors of fair-skinned people, there have been very few studies on the distribution of αE(CD103)β7 expressing cells in these neoplasms. Given this background, we describe here that αE(CD103)β7 is scarcely present in basal cell carcinomas, but much more abundant in squamous cell carcinomas with heterogeneous distribution. Notwithstanding a substantial number of studies, the role of αE(CD103)β7 in the tumor context is still far from clear. Here, we summarize the essential current knowledge on αE(CD103)β7 and outline that it is worthwhile to further explore this intriguing receptor with regard to the pathophysiology, therapy, and prognosis of solid tumors.
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Affiliation(s)
- Johanna C. Hoffmann
- Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, 37075 Göttingen, Germany;
| | - Michael P. Schön
- Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, 37075 Göttingen, Germany;
- Lower Saxony Institute of Occupational Dermatology, University Medical Center Göttingen, 37075 Göttingen, Germany
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5
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Emmanuel T, Mistegård J, Bregnhøj A, Johansen C, Iversen L. Tissue-Resident Memory T Cells in Skin Diseases: A Systematic Review. Int J Mol Sci 2021; 22:ijms22169004. [PMID: 34445713 PMCID: PMC8396505 DOI: 10.3390/ijms22169004] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 08/09/2021] [Accepted: 08/17/2021] [Indexed: 02/06/2023] Open
Abstract
In health, the non-recirculating nature and long-term persistence of tissue-resident memory T cells (TRMs) in tissues protects against invading pathogens. In disease, pathogenic TRMs contribute to the recurring traits of many skin diseases. We aimed to conduct a systematic literature review on the current understanding of the role of TRMs in skin diseases and identify gaps as well as future research paths. EMBASE, PubMed, SCOPUS, Web of Science, Clinicaltrials.gov and WHO Trials Registry were searched systematically for relevant studies from their inception to October 2020. Included studies were reviewed independently by two authors. This study was conducted in accordance with the PRISMA-S guidelines. This protocol was registered with the PROSPERO database (ref: CRD42020206416). We identified 96 studies meeting the inclusion criteria. TRMs have mostly been investigated in murine skin and in relation to infectious skin diseases. Pathogenic TRMs have been characterized in various skin diseases including psoriasis, vitiligo and cutaneous T-cell lymphoma. Studies are needed to discover biomarkers that may delineate TRMs poised for pathogenic activity in skin diseases and establish to which extent TRMs are contingent on the local skin microenvironment. Additionally, future studies may investigate the effects of current treatments on the persistence of pathogenic TRMs in human skin.
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Hochheiser K, Wiede F, Wagner T, Freestone D, Enders MH, Olshansky M, Russ B, Nüssing S, Bawden E, Braun A, Bachem A, Gressier E, McConville R, Park SL, Jones CM, Davey GM, Gyorki DE, Tscharke D, Parish IA, Turner S, Herold MJ, Tiganis T, Bedoui S, Gebhardt T. Ptpn2 and KLRG1 regulate the generation and function of tissue-resident memory CD8+ T cells in skin. J Exp Med 2021; 218:212037. [PMID: 33914023 PMCID: PMC8091133 DOI: 10.1084/jem.20200940] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 12/21/2020] [Accepted: 02/10/2021] [Indexed: 12/30/2022] Open
Abstract
Tissue-resident memory T cells (TRM cells) are key elements of tissue immunity. Here, we investigated the role of the regulator of T cell receptor and cytokine signaling, Ptpn2, in the formation and function of TRM cells in skin. Ptpn2-deficient CD8+ T cells displayed a marked defect in generating CD69+ CD103+ TRM cells in response to herpes simplex virus type 1 (HSV-1) skin infection. This was accompanied by a reduction in the proportion of KLRG1− memory precursor cells and a transcriptional bias toward terminal differentiation. Of note, forced expression of KLRG1 was sufficient to impede TRM cell formation. Normalizing memory precursor frequencies by transferring equal numbers of KLRG1− cells restored TRM generation, demonstrating that Ptpn2 impacted skin seeding with precursors rather than downstream TRM cell differentiation. Importantly, Ptpn2-deficient TRM cells augmented skin autoimmunity but also afforded superior protection from HSV-1 infection. Our results emphasize that KLRG1 repression is required for optimal TRM cell formation in skin and reveal an important role of Ptpn2 in regulating TRM cell functionality.
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Affiliation(s)
- Katharina Hochheiser
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia.,Peter MacCallum Cancer Centre Melbourne, Melbourne, Victoria, Australia
| | - Florian Wiede
- Peter MacCallum Cancer Centre Melbourne, Melbourne, Victoria, Australia.,Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
| | - Teagan Wagner
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
| | - David Freestone
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
| | - Matthias H Enders
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
| | - Moshe Olshansky
- Department of Microbiology, Monash University, Clayton, Victoria, Australia
| | - Brendan Russ
- Department of Microbiology, Monash University, Clayton, Victoria, Australia
| | - Simone Nüssing
- Peter MacCallum Cancer Centre Melbourne, Melbourne, Victoria, Australia.,Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia
| | - Emma Bawden
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
| | - Asolina Braun
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
| | - Annabell Bachem
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
| | - Elise Gressier
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
| | - Robyn McConville
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
| | - Simone L Park
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
| | - Claerwen M Jones
- Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
| | - Gayle M Davey
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
| | - David E Gyorki
- Peter MacCallum Cancer Centre Melbourne, Melbourne, Victoria, Australia.,Department of Surgery, University of Melbourne, Parkville, Victoria, Australia
| | - David Tscharke
- The John Curtin School of Medical Research, The Australian National University, Acton, Australian Capital Territory, Australia
| | - Ian A Parish
- Peter MacCallum Cancer Centre Melbourne, Melbourne, Victoria, Australia.,Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia
| | - Stephen Turner
- Department of Microbiology, Monash University, Clayton, Victoria, Australia
| | - Marco J Herold
- The Walter & Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia.,Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia
| | - Tony Tiganis
- Peter MacCallum Cancer Centre Melbourne, Melbourne, Victoria, Australia.,Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
| | - Sammy Bedoui
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
| | - Thomas Gebhardt
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
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7
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Toh JWT, Ferguson AL, Spring KJ, Mahajan H, Palendira U. Cytotoxic CD8+ T cells and tissue resident memory cells in colorectal cancer based on microsatellite instability and BRAF status. World J Clin Oncol 2021; 12:238-248. [PMID: 33959477 PMCID: PMC8085513 DOI: 10.5306/wjco.v12.i4.238] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 03/14/2021] [Accepted: 04/05/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Recent studies in non-colorectal malignancy have associated T resident memory (TRM) cells with improved patient survival. It is unknown if TRM plays a role in colorectal cancer (CRC).
AIM To examine the potential role of TRM cells in providing immunogenicity in CRC stratified by microsatellite instability (MSI) and BRAF status.
METHODS Patients with known MSI and BRAF mutation status were eligible for inclusion in this study. CRC tumour sections stained with haematoxylin and eosin were microscopically reviewed and the images scanned prior to assessment for location of invading edge and core of tumour. Sequential sections were prepared for quantitative multiplex immunohistochemistry (IHC) staining. Opal Multiplex IHC staining was performed with appropriate positive and negative controls and imaged using a standard fluorescent microscope fitted with a spectral scanning camera (Mantra) in conjunction with Mantra snap software. Images were unmixed and annotated in inForm 2.2.0. Statistical analysis was performed using Graphpad Prism Version 7 and Stata Version 15.
RESULTS Seventy-two patients with known MSI and BRAF status were included in the study. All patients were assessed for MSI by IHC and high resolution capillary electrophoresis testing and 44 of these patients successfully underwent quantitative multiplex IHC staining. Overall, there was a statistically significant increase in CD8+ TRM cells in the MSI (BRAF mutant and wild type) group over the microsatellite stable (MSS) group. There was a statistically significant difference in CD8+ TRM between high level MSI (MSI-H):BRAF mutant [22.57, 95% confidence interval (CI): 14.31-30.84] vs MSS [8.031 (95%CI: 4.698-11.36)], P = 0.0076 andMSI-H:BRAF wild type [16.18 (95%CI: 10.44-21.93)] vs MSS [8.031 (95%CI: 4.698-11.36)], P = 0.0279. There was no statistically significant difference in CD8 T cells (both CD8+CD103- and CD8+CD103+TRM) between MSI-H: BRAF mutant and wild type CRC.
CONCLUSION This study has shown that CD8+ TRM are found in greater abundance in MSI-H CRC, both BRAF mutant and MSI-H:BRAF wild type, when compared with their MSS counterpart. CD8+ TRM may play a role in the immunogenicity in MSI-H CRC (BRAF mutant and BRAF wild type). Further studies should focus on the potential immunogenic qualities of TRM cells and investigate potential immunotherapeutic approaches to improve treatment and survival associated with CRC.
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Affiliation(s)
- James Wei Tatt Toh
- Division of Surgery and Anaesthesia, Department of Colorectal Surgery, Westmead Hospital, Westmead Clinical School, The University of Sydney, Ingham Institute for Applied Medical Research, Westmead 2145, NSW, Australia
| | - Angela L Ferguson
- Department of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine and Health, Human Viral & Cancer Immunology, Centenary Institute, Charles Perkin Centre, The University of Sydney, Sydney 2000, NSW, Australia
| | - Kevin J Spring
- Medical Oncology Group, Ingham Institute for Applied Medical Research, Liverpool Hospital, Liverpool Clinical School, University of Western Sydney, South Western Clinical School UNSW, Liverpool 2170, NSW, Australia
| | - Hema Mahajan
- Department of Anatomical Pathology, ICPMR, Westmead Hospital, Westmead 2145, NSW, Australia
| | - Umaimainthan Palendira
- Department of Immunology and Infectious Diseases, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney 2000, NSW, Australia
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8
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Carrié L, Virazels M, Dufau C, Montfort A, Levade T, Ségui B, Andrieu-Abadie N. New Insights into the Role of Sphingolipid Metabolism in Melanoma. Cells 2020; 9:E1967. [PMID: 32858889 PMCID: PMC7565650 DOI: 10.3390/cells9091967] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 08/22/2020] [Accepted: 08/24/2020] [Indexed: 12/21/2022] Open
Abstract
Cutaneous melanoma is a deadly skin cancer whose aggressiveness is directly linked to its metastatic potency. Despite remarkable breakthroughs in term of treatments with the emergence of targeted therapy and immunotherapy, the prognosis for metastatic patients remains uncertain mainly because of resistances. Better understanding the mechanisms responsible for melanoma progression is therefore essential to uncover new therapeutic targets. Interestingly, the sphingolipid metabolism is dysregulated in melanoma and is associated with melanoma progression and resistance to treatment. This review summarises the impact of the sphingolipid metabolism on melanoma from the initiation to metastatic dissemination with emphasis on melanoma plasticity, immune responses and resistance to treatments.
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Affiliation(s)
- Lorry Carrié
- Centre de Recherches en Cancérologie de Toulouse, Equipe Labellisée Fondation ARC, Université Fédérale de Toulouse Midi-Pyrénées, Université Toulouse III Paul-Sabatier, Inserm 1037, 2 avenue Hubert Curien, CS 53717, 31037 Toulouse CEDEX 1, France; (L.C.); (M.V.); (C.D.); (A.M.); (T.L.); (B.S.)
| | - Mathieu Virazels
- Centre de Recherches en Cancérologie de Toulouse, Equipe Labellisée Fondation ARC, Université Fédérale de Toulouse Midi-Pyrénées, Université Toulouse III Paul-Sabatier, Inserm 1037, 2 avenue Hubert Curien, CS 53717, 31037 Toulouse CEDEX 1, France; (L.C.); (M.V.); (C.D.); (A.M.); (T.L.); (B.S.)
| | - Carine Dufau
- Centre de Recherches en Cancérologie de Toulouse, Equipe Labellisée Fondation ARC, Université Fédérale de Toulouse Midi-Pyrénées, Université Toulouse III Paul-Sabatier, Inserm 1037, 2 avenue Hubert Curien, CS 53717, 31037 Toulouse CEDEX 1, France; (L.C.); (M.V.); (C.D.); (A.M.); (T.L.); (B.S.)
| | - Anne Montfort
- Centre de Recherches en Cancérologie de Toulouse, Equipe Labellisée Fondation ARC, Université Fédérale de Toulouse Midi-Pyrénées, Université Toulouse III Paul-Sabatier, Inserm 1037, 2 avenue Hubert Curien, CS 53717, 31037 Toulouse CEDEX 1, France; (L.C.); (M.V.); (C.D.); (A.M.); (T.L.); (B.S.)
| | - Thierry Levade
- Centre de Recherches en Cancérologie de Toulouse, Equipe Labellisée Fondation ARC, Université Fédérale de Toulouse Midi-Pyrénées, Université Toulouse III Paul-Sabatier, Inserm 1037, 2 avenue Hubert Curien, CS 53717, 31037 Toulouse CEDEX 1, France; (L.C.); (M.V.); (C.D.); (A.M.); (T.L.); (B.S.)
- Laboratoire de Biochimie Métabolique, CHU, 31059 Toulouse, France
| | - Bruno Ségui
- Centre de Recherches en Cancérologie de Toulouse, Equipe Labellisée Fondation ARC, Université Fédérale de Toulouse Midi-Pyrénées, Université Toulouse III Paul-Sabatier, Inserm 1037, 2 avenue Hubert Curien, CS 53717, 31037 Toulouse CEDEX 1, France; (L.C.); (M.V.); (C.D.); (A.M.); (T.L.); (B.S.)
| | - Nathalie Andrieu-Abadie
- Centre de Recherches en Cancérologie de Toulouse, Equipe Labellisée Fondation ARC, Université Fédérale de Toulouse Midi-Pyrénées, Université Toulouse III Paul-Sabatier, Inserm 1037, 2 avenue Hubert Curien, CS 53717, 31037 Toulouse CEDEX 1, France; (L.C.); (M.V.); (C.D.); (A.M.); (T.L.); (B.S.)
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