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Yao RR, Zhang QB, Ge MX, Li L, Li J, Zhou XL, Wang ZX, Liang XH. The safety and efficacy of atezolizumab for recurrent primary liver cancer after liver transplantation. Discov Oncol 2025; 16:553. [PMID: 40244542 PMCID: PMC12006625 DOI: 10.1007/s12672-025-02299-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Accepted: 04/02/2025] [Indexed: 04/18/2025] Open
Abstract
BACKGROUND Immune checkpoint inhibitors (ICIs) have been proved to have certain therapeutic effects for primary liver cancer. However, the efficacy and safety of their applications in liver transplantation (LT) recipients with recurrent tumor remained unclear and even controversial. METHODS A retrospective study was conducted to evaluate the safety and efficacy of atezolizumab in LT recipients with recurrent PLC from August 1, 2019, to July 1, 2022. The primary endpoint was the incidence of allograft rejection, while secondary endpoints included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Additionally, risk factors associated with ICI-related rejection were analyzed. RESULTS A total of eight LT recipients with recurrent PLC were included in the study, comprising six cases of hepatocellular carcinoma (HCC) and two cases of intrahepatic cholangiocarcinoma (ICC). The median number of atezolizumab treatment cycles was 3 (range, 1-10). Graft rejection occurred in 25% of patients (2/8). The median overall survival (mOS) from the initiation of atezolizumab was 6.2 months (range, 0.7-12.5 months), with a mortality rate of 75% (6/8). The ORR (complete response [CR] + partial response [PR]) was 28.5% (2/7), and the disease control rate (DCR; CR + PR + stable disease [SD]) was 42.9% (3/7). Time from LT to recurrence (P = 0.008) and Interval time from LT to atezolizumab (P = 0.005) were associated with liver rejection. CONCLUSIONS Atezolizumab demonstrated a certain degree of efficacy as a salvage treatment for patients with recurrent HCC and ICC after LT. However, given the potential risk of allograft rejection, careful evaluation of safety is essential before initiating ICI therapy. Moreover, close monitoring and timely intervention are necessary during treatment to mitigate the risk of rejection. Future studies should further explore the optimal timing and strategies for ICI administration in this patient population.
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Grants
- (2020QD010) Scientific Research Foundation of Huashan Hospital, Fudan University
- (2020QD010) Scientific Research Foundation of Huashan Hospital, Fudan University
- (2020QD010) Scientific Research Foundation of Huashan Hospital, Fudan University
- (2020QD010) Scientific Research Foundation of Huashan Hospital, Fudan University
- (2020QD010) Scientific Research Foundation of Huashan Hospital, Fudan University
- 82071797, 82173093, 82241225 Natural Science Foundation of China
- 82071797, 82173093, 82241225 Natural Science Foundation of China
- 82071797, 82173093, 82241225 Natural Science Foundation of China
- (SHDC2020CR2021B) the Shanghai Hospital Development Center
- (SHDC2020CR2021B) the Shanghai Hospital Development Center
- (SHDC2020CR2021B) the Shanghai Hospital Development Center
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Affiliation(s)
- Rong-Rong Yao
- Department of Oncology, Huashan Hospital, Fudan University, 12 Urumqi Road(M), Shanghai, 200040, China
| | - Quan-Bao Zhang
- Liver Transplantation Center, Department of General Surgery, Huashan Hospital, Fudan University, 12 Urumqi Road(M), Shanghai, 200040, China
- Institute of Organ Transplantation, Fudan University, 12 Urumqi Road(M), Shanghai, 200040, China
| | - Meng-Xi Ge
- Department of Oncology, Huashan Hospital, Fudan University, 12 Urumqi Road(M), Shanghai, 200040, China
| | - Li Li
- Liver Transplantation Center, Department of General Surgery, Huashan Hospital, Fudan University, 12 Urumqi Road(M), Shanghai, 200040, China
- Institute of Organ Transplantation, Fudan University, 12 Urumqi Road(M), Shanghai, 200040, China
| | - Jing Li
- Department of Oncology, Huashan Hospital, Fudan University, 12 Urumqi Road(M), Shanghai, 200040, China
| | - Xin-Li Zhou
- Department of Oncology, Huashan Hospital, Fudan University, 12 Urumqi Road(M), Shanghai, 200040, China
| | - Zheng-Xin Wang
- Liver Transplantation Center, Department of General Surgery, Huashan Hospital, Fudan University, 12 Urumqi Road(M), Shanghai, 200040, China.
- Institute of Organ Transplantation, Fudan University, 12 Urumqi Road(M), Shanghai, 200040, China.
| | - Xiao-Hua Liang
- Department of Oncology, Huashan Hospital, Fudan University, 12 Urumqi Road(M), Shanghai, 200040, China.
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Hong G, Han DK, Rhu J, Hong SK, Choi Y, Yi NJ, Lee KW, Kim J, Yang J, Suh KS. Safety and Therapeutic Outcomes of Adjuvant Immunotherapy With Autologous Cytokine-induced Killer Cells for Patients With Hepatocellular Carcinoma Beyond Milan Criteria After Liver Transplantation. Transplantation 2025:00007890-990000000-01062. [PMID: 40235029 DOI: 10.1097/tp.0000000000005406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/17/2025]
Abstract
BACKGROUND Adjuvant immunotherapy with autologous cytokine-induced killer (CIK) cells for hepatocellular carcinoma (HCC) remains understudied in liver transplant patients because of potential risks of acute rejection and diminished efficacy by immunosuppression. METHODS This study examined the safety and effectiveness of CIK therapy in patients with HCC exceeding the Milan criteria, treated at 2 Korean hospitals between 2019 and 2021. We analyzed clinical outcomes of 16 patients who underwent CIK therapy compared with 44 propensity-matched controls who did not receive CIK therapy. CIK cells were administered in 6 escalating doses, either 3 or 6 times over the course of weeks 4, 5, 6, 8, 10, and 12 posttransplantation. RESULTS CIK therapy was well-tolerated without significant treatment-related adverse reactions. Maximal tolerated dose of CIK cells was 10 × 109, which had been repeated 6 times. The CIK group exhibited higher 2-y HCC recurrence-free (87.5% versus 62.9%, P = 0.027) and patient survival (100% versus 81.5%, P = 0.002) rates, with no significant difference in rejection-free survival rates (92.9% versus 95.0%, P = 0.926) compared with the no-CIK group. Subgroup analysis showed that the CIK group in patients with high retreat scores, elevated R3-α-fetoprotein scores, and those beyond the University of California San Francisco criteria had improved HCC recurrence-free survival. Immunological evaluation showed elevated CD8+ T cells and polymorphonuclear myeloid-derived suppressor cells with transient increases in granzyme B and tumor necrosis factor-α levels in the CIK group. CONCLUSIONS These findings advocate CIK therapy as a safe and effective, potential adjuvant treatment for HCC beyond Milan criteria after transplantation, supporting further validation trials.
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Affiliation(s)
- Geun Hong
- Graduate School of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Surgery, EWHA Womans University College of Medicine, Seoul, Republic of Korea
| | - Dong Kyu Han
- Graduate School of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Biomedical Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Suk Kyun Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jongman Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jaeseok Yang
- Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea
| | - Kyung-Suk Suh
- Graduate School of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
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Lau G, Obi S, Zhou J, Tateishi R, Qin S, Zhao H, Otsuka M, Ogasawara S, George J, Chow PKH, Cai J, Shiina S, Kato N, Yokosuka O, Oura K, Yau T, Chan SL, Kuang M, Ueno Y, Chen M, Cheng AL, Cheng G, Chuang WL, Baatarkhuu O, Bi F, Dan YY, Gani RA, Tanaka A, Jafri W, Jia JD, Kao JH, Hasegawa K, Lau P, Lee JM, Liang J, Liu Z, Lu Y, Pan H, Payawal DA, Rahman S, Seong J, Shen F, Shiha G, Song T, Sun HC, Masaki T, Sirachainan E, Wei L, Yang JM, Sallano JD, Zhang Y, Tanwandee T, Dokmeci AK, Zheng SS, Fan J, Fan ST, Sarin SK, Omata M. APASL clinical practice guidelines on systemic therapy for hepatocellular carcinoma-2024. Hepatol Int 2024; 18:1661-1683. [PMID: 39570557 DOI: 10.1007/s12072-024-10732-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 09/16/2024] [Indexed: 11/22/2024]
Abstract
In Asia-Pacific region, hepatocellular carcinoma is a serious health threat attributing to over 600,000 deaths each year and account for over 70% of global cases. Clinically, the major unmet needs are recurrence after curative-intent surgery, liver transplantation or local ablation and disease progression in those with hepatocellular carcinoma not eligible for resection or failed locoregional therapy. In the recent few years, new targeted therapy and immune-checkpoint inhibitors have been registered as systemic therapy to address these issues. Notably, new forms of systemic therapy, either as first-line or second-line therapy for unresectable hepatocellular or those not eligible for locoregional therapy, are now available. New data is also emerging with the use of systemic therapy to prevent hepatocellular carcinoma recurrence after curative-intent resection or local ablation therapy and to retard disease progression after locoregional therapy. In the future, further implementation of immune-checkpoint inhibitors and other forms of immunotherapy are expected to bring a new paradigm to the management of hepatocellular carcinoma. New insight related to immune-related adverse events with the use of immunotherapy has allso enabled optimization of the therapeutic approach to patients with hepatocellular carcinoma. The purpose of this clinical practice guideline is to provide an up-to-date recommendation based on clinical evidence and experience from expert Asia-Pacific key opinion leaders in the field of hepatocellular carcinoma. Three key questions will be addressed, namely: (1) Which patients with hepatocellular carcinoma should be considered for systemic therapy? (2) Which systemic therapy should be used? (3) How should a patient planned for immune checkpoint-based systemic therapy be managed and monitored?
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Affiliation(s)
- George Lau
- Humanity and Health Clinical Trial Center, Humanity and Health Medical Group, Zhongshan Hospital, Fudan University, Hong Kong SAR, Shanghai, China.
| | - Shuntaro Obi
- Department of Internal Medicine, Teikyo University Chiba Medical Center, Chiba, Japan
| | - Jian Zhou
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai Key Laboratory of Organ Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Shukui Qin
- Cancer Centre of Jinling Hospital, Nanjing University of Chinese Medicine, Nanjing, China
| | - Haitao Zhao
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Motoyuki Otsuka
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, 700-8558, Japan
| | - Sadahisa Ogasawara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, 2145, Australia
| | - Pierce K H Chow
- Department of HPB Surgery and Transplantation, Duke-NUS Medical School, National Cancer Center Singapore and Singapore General Hospital, Surgery Academic Clinical Program, Singapore, Singapore
| | - Jianqiang Cai
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shuichiro Shiina
- Department of Gastroenterology, Juntendo University, 2-1-1, Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Naoya Kato
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Kyoko Oura
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Kita, Miki, Kagawa, 761-0793, Japan
| | - Thomas Yau
- Department of Medicine, The University of Hong Kong, Hong Kong, China
| | - Stephen L Chan
- Department of Clinical Oncology, State Key Laboratory of Translational Oncology, Sir YK Pao Centre for Cancer, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Ming Kuang
- Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yoshiyuki Ueno
- Faculty of Medicine, Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan
| | - Minshan Chen
- Department of Liver Surgery, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Ann-Lii Cheng
- Department of OncologyDepartment of Medical OncologyGraduate Institute of OncologyDepartment of Internal Medicine, National Taiwan University Cancer CenterNational Taiwan University HospitalNational Taiwan University College of Medicine, Taipei, Taiwan
| | - Gregory Cheng
- Humanity and Health Clinical Trial Center, Humanity & Health Medical Group, Hong Kong SAR, China
- Faculty of Health Science, Macau University, Macau SAR, China
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Center for Infectious Disease and Cancer Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Oidov Baatarkhuu
- School of Medicine, Mongolian National University of Medical Sciences, Ulan Bator, Mongolia
| | - Feng Bi
- Department of Medical Oncology, Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Yock Young Dan
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
| | - Rino A Gani
- Hepatobiliary Division, Staff Medic Group of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo Hospital, Jakarta, 10430, Indonesia
| | - Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Wasim Jafri
- The Aga Khan University Hospital, Karachi, Pakistan
| | - Ji-Dong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jia-Horng Kao
- Department of Internal Medicine Division of Gastroenterology and Hepatology, Department of Internal MedicineHepatitis Research Center, Graduate Institute of Clinical Medicine, National Taiwan University Hospital Bei-Hu BranchNational Taiwan University HospitalNational Taiwan University College of Medicine, Taipei, Taiwan
| | - Kiyoshi Hasegawa
- Department of Surgery, Graduate School of Medicine, Hepato-Biliary-Pancreatic Surgery Division, The University of Tokyo, Tokyo, Japan
| | - Patrick Lau
- Humanity and Health Clinical Trial Center, Humanity & Health Medical Group, Hong Kong SAR, China
| | - Jeong Min Lee
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Jun Liang
- Department of Medical Oncology, Peking University International Hospital, Beijing, China
| | - Zhenwen Liu
- Senior Department of Hepatology, The Fifth Medical Center of Chinese People's Liberation, Army General Hospital, Beijing, China
| | - Yinying Lu
- Department of Comprehensive Liver Cancer Center, The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, China
| | - Hongming Pan
- Department of Medical Oncology, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Diana A Payawal
- Department of Medicine, Fatima University Medical Center, Manila, Philippines
| | - Salimur Rahman
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, 1000, Bangladesh
| | - Jinsil Seong
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Gamal Shiha
- European Liver Patients' Association (ELPA), Brussels, Belgium
- World Hepatitis Alliance, London, UK
- African Liver Patient Association (ALPA), Cairo, Egypt
- The Association of Liver Patients Care (ALPC), Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Egyptian Liver Research Institute and Hospital (ELRIAH), Sherbin, El Mansoura, Egypt
| | - Tianqiang Song
- Department of Hepatobiliary, HCC Research Center for Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China
| | - Hui-Chuan Sun
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Kita, Miki, Kagawa, 761-0793, Japan
| | - Ekaphop Sirachainan
- Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Lai Wei
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Jose D Sallano
- Section of Gastroenterology, University of Santo Tomas, Manila, Philippines
| | - Yanqiao Zhang
- Department of Gastrointestinal Medical Oncology, Institute of Prevention and Treatment of Cancer of Heilongjiang Province, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
| | - Tawesak Tanwandee
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - AKadir Dokmeci
- Department of Medicine, Ankara University School of Medicine, Ankara, Turkey
| | - Shu-Sen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou, China
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Sheung-Tat Fan
- Liver Surgery and Transplant Centre, Hong Kong Sanatorium and Hospital, Hong Kong, Japan
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Prefectural Center Hospital, Kofu-City, Yamanashi, Japan
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Tabrizian P, Zeitlhoefler M, Hassan AT, Marino R. Immunotherapy for transplantation of hepatocellular carcinoma: the next frontier in adjunctive therapy. Curr Opin Organ Transplant 2024; 29:144-154. [PMID: 38164882 DOI: 10.1097/mot.0000000000001133] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2024]
Abstract
PURPOSE OF REVIEW The increasing success of liver transplantation in hepatocellular carcinoma (HCC) drives an ever-evolving search for innovative strategies to broaden eligible patients' pools. Recent advances in immuno-oncology have turned the spotlight on immune checkpoint inhibitors (ICIs). This review offers an updated overview of ICIs in liver transplantation for HCC, exploring neoadjuvant and adjuvant approaches and addressing unanswered questions on safety, patients' selection, and response predictors. RECENT FINDINGS ICIs have transitioned from being a last-chance therapeutic hope to becoming an integral cornerstone in the treatment of advanced HCC, holding great promise as a compelling option not only to downstage patients for transplantation but also as an alternative strategy in addressing posttransplantation disease recurrence. Despite ongoing refinements in immunotherapeutic agents, the complex molecular pathways involved emphasize the need for a comprehensive approach to integrate immunotherapy in liver transplantation. SUMMARY Initial concerns about graft rejection, with ICIs as a bridging therapy to liver transplantation, were successfully addressed using adequate immunosuppressants strategies and minimized with a sufficient washout period. Post-liver transplantation disease recurrence remains challenging, requiring a balance between effective therapy and preserving graft function. Emphasis should be placed on clinical trials validating the risk-benefit ratio of ICIs for liver transplantation, guiding appropriate patients' selection, and establishing clear management pathways.
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Affiliation(s)
- Parissa Tabrizian
- Liver Transplant and Hepatobiliary Surgery, Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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Fortuny M, Sanduzzi-Zamparelli M, Reig M. Systemic therapies in hepatocellular carcinoma: A revolution? United European Gastroenterol J 2024; 12:252-260. [PMID: 38267015 PMCID: PMC10954433 DOI: 10.1002/ueg2.12510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Accepted: 11/06/2023] [Indexed: 01/26/2024] Open
Abstract
The evolution in systemic therapies in hepatocellular carcinoma (HCC) signifies a strategy of high-cost, high-gain innovation that originated with sorafenib, despite its limited impact on tumor response. This strategic approach paved the way for the emergence of a second wave of the short-lived competitive advantage, exemplified by the incorporation of atezolizumab plus bevacizumab and tremelimumab plus durvalumab. In the context of safety concerns within the liver cancer domain, the IMBRAVE150 and HIMALAYA trials boldly incorporated bevacizumab and tremelimumab, respectively, demonstrating the continuation of the high-risk, high-reward innovation paradigm. This review delves into the strengths, weaknesses, opportunities, and threats analysis of systemic therapies in the field of HCC.
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Affiliation(s)
- Marta Fortuny
- Barcelona Clinic Liver Cancer (BCLC) Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Liver Oncology Unit, Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Marco Sanduzzi-Zamparelli
- Barcelona Clinic Liver Cancer (BCLC) Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Liver Oncology Unit, Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Maria Reig
- Barcelona Clinic Liver Cancer (BCLC) Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Liver Oncology Unit, Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Barcelona University, Barcelona, Spain
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Abdelrahim M, Esmail A, Abudayyeh A, Murakami N, Victor D, Kodali S, Cheah YL, Simon CJ, Noureddin M, Connor A, Saharia A, Moore LW, Heyne K, Kaseb AO, Gaber AO, Ghobrial RM. Transplant Oncology: An Emerging Discipline of Cancer Treatment. Cancers (Basel) 2023; 15:5337. [PMID: 38001597 PMCID: PMC10670243 DOI: 10.3390/cancers15225337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 10/30/2023] [Indexed: 11/26/2023] Open
Abstract
Transplant oncology is an emerging concept of cancer treatment with a promising prospective outcome. The applications of oncology, transplant medicine, and surgery are the core of transplant oncology to improve patients' survival and quality of life. The main concept of transplant oncology is to radically cure cancer by removing the diseased organ and replacing it with a healthy one, aiming to improve the survival outcomes and quality of life of cancer patients. Subsequently, it seeks to expand the treatment options and research for hepatobiliary malignancies, which have seen significantly improved survival outcomes after the implementation of liver transplantation (LT). In the case of colorectal cancer (CRC) in the transplant setting, where the liver is the most common site of metastasis of patients who are considered to have unresectable disease, initial studies have shown improved survival for LT treatment compared to palliative therapy interventions. The indications of LT for hepatobiliary malignancies have been slowly expanded over the years beyond Milan criteria in a stepwise manner. However, the outcome improvements and overall patient survival are limited to the specifics of the setting and systematic intervention options. This review aims to illustrate the representative concepts and history of transplant oncology as an emerging discipline for the management of hepatobiliary malignancies, in addition to other emerging concepts, such as the uses of immunotherapy in a peri-transplant setting as well as the use of circulating tumor DNA (ctDNA) for surveillance post-transplantation.
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Affiliation(s)
- Maen Abdelrahim
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (A.E.)
- Cockrell Center of Advanced Therapeutics Phase I Program, Houston Methodist Research Institute, Houston, TX 77030, USA
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Abdullah Esmail
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (A.E.)
| | - Ala Abudayyeh
- Section of Nephrology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Naoka Murakami
- Division of Renal Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA;
| | - David Victor
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Sudha Kodali
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Yee Lee Cheah
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Caroline J. Simon
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Mazen Noureddin
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Ashton Connor
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Ashish Saharia
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Linda W. Moore
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Kirk Heyne
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (A.E.)
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Ahmed O. Kaseb
- Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - A. Osama Gaber
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Rafik Mark Ghobrial
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
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7
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Montano-Loza AJ, Rodríguez-Perálvarez ML, Pageaux GP, Sanchez-Fueyo A, Feng S. Liver transplantation immunology: Immunosuppression, rejection, and immunomodulation. J Hepatol 2023; 78:1199-1215. [PMID: 37208106 DOI: 10.1016/j.jhep.2023.01.030] [Citation(s) in RCA: 71] [Impact Index Per Article: 35.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 12/30/2022] [Accepted: 01/30/2023] [Indexed: 05/21/2023]
Abstract
Outcomes after liver transplantation have continuously improved over the past decades, but long-term survival rates are still lower than in the general population. The liver has distinct immunological functions linked to its unique anatomical configuration and to its harbouring of a large number of cells with fundamental immunological roles. The transplanted liver can modulate the immunological system of the recipient to promote tolerance, thus offering the potential for less aggressive immunosuppression. The selection and adjustment of immunosuppressive drugs should be individualised to optimally control alloreactivity while mitigating toxicities. Routine laboratory tests are not accurate enough to make a confident diagnosis of allograft rejection. Although several promising biomarkers are being investigated, none of them is sufficiently validated for routine use; hence, liver biopsy remains necessary to guide clinical decisions. Recently, there has been an exponential increase in the use of immune checkpoint inhibitors due to the unquestionable oncological benefits they provide for many patients with advanced-stage tumours. It is expected that their use will also increase in liver transplant recipients and that this might affect the incidence of allograft rejection. Currently, the evidence regarding the efficacy and safety of immune checkpoint inhibitors in liver transplant recipients is limited and cases of severe allograft rejection have been reported. In this review, we discuss the clinical relevance of alloimmune disease, the role of minimisation/withdrawal of immunosuppression, and provide practical guidance for using checkpoint inhibitors in liver transplant recipients.
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Affiliation(s)
- Aldo J Montano-Loza
- Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, AB, Canada.
| | - Manuel L Rodríguez-Perálvarez
- Department of Hepatology and Liver Transplantation, Hospital Universitario Reina Sofía, Universidad de Córdoba, IMIBIC, Córdoba, Spain; CIBER de Enfermedades Hepáticas y Digestivas, Madrid, Spain
| | - George-Philippe Pageaux
- Liver Transplantation Unit, Digestive Department, Saint Eloi University Hospital, University of Montpellier, 34295, Montpellier Cedex 5, France
| | - Alberto Sanchez-Fueyo
- Institute of Liver Studies, King's College London University and King's College Hospital, London, United Kingdom
| | - Sandy Feng
- Department of Surgery, University of California San Francisco, San Francisco, CA, USA
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8
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Gao YX, Ning QQ, Yang PX, Guan YY, Liu PX, Liu ML, Qiao LX, Guo XH, Yang TW, Chen DX. Recent advances in recurrent hepatocellular carcinoma therapy. World J Hepatol 2023; 15:460-476. [PMID: 37206651 PMCID: PMC10190692 DOI: 10.4254/wjh.v15.i4.460] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 12/20/2022] [Accepted: 03/24/2023] [Indexed: 04/20/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer, accounting for 75%-85% of cases. Although treatments are given to cure early-stage HCC, up to 50%-70% of individuals may experience a relapse of the illness in the liver after 5 years. Research on the fundamental treatment modalities for recurrent HCC is moving significantly further. The precise selection of individuals for therapy strategies with established survival advantages is crucial to ensuring better outcomes. These strategies aim to minimize substantial morbidity, support good life quality, and enhance survival for patients with recurrent HCC. For individuals with recurring HCC after curative treatment, no approved therapeutic regimen is currently available. A recent study presented novel approaches, like immunotherapy and antiviral medication, to improve the prognosis of patients with recurring HCC with the apparent lack of data to guide the clinical treatment. The data supporting several neoadjuvant and adjuvant therapies for patients with recurring HCC are outlined in this review. We also discuss the potential for future clinical and translational investigations.
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Affiliation(s)
- Yu-Xue Gao
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Qi-Qi Ning
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Peng-Xiang Yang
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Yuan-Yue Guan
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Peng-Xiang Liu
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Meng-Lu Liu
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Lu-Xin Qiao
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Xiang-Hua Guo
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Tong-Wang Yang
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Academician Workstation, Changsha Medical University, Changsha 410219, Hunan Province, China
- Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha 410219, Hunan Province, China
| | - De-Xi Chen
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
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9
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Jiang J, Huang H, Chen R, Lin Y, Ling Q. Immunotherapy for hepatocellular carcinoma recurrence after liver transplantation, can we harness the power of immune checkpoint inhibitors? Front Immunol 2023; 14:1092401. [PMID: 36875077 PMCID: PMC9978931 DOI: 10.3389/fimmu.2023.1092401] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 02/03/2023] [Indexed: 02/18/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death globally and liver transplantation (LT) can serve as the best curative treatment option. However, HCC recurrence after LT remains the major obstacle to the long-term survival of recipients. Recently, immune checkpoint inhibitors (ICIs) have revolutionized the treatment of many cancers and provided a new treatment strategy for post-LT HCC recurrence. Evidence has been accumulated with the real-world application of ICIs in patients with post-LT HCC recurrence. Notably, the use of these agents as immunity boosters in recipients treated with immunosuppressors is still controversial. In this review, we summarized the immunotherapy for post-LT HCC recurrence and conducted an efficacy and safety evaluation based on the current experience of ICIs for post-LT HCC recurrence. In addition, we further discussed the potential mechanism of ICIs and immunosuppressive agents in regulating the balance between immune immunosuppression and lasting anti-tumor immunity.
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Affiliation(s)
- Jingyu Jiang
- Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- National Health Commission (NHC) Key Laboratory of Combined Multi-Organ Transplantation, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Haitao Huang
- Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- National Health Commission (NHC) Key Laboratory of Combined Multi-Organ Transplantation, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Ruihan Chen
- Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- National Health Commission (NHC) Key Laboratory of Combined Multi-Organ Transplantation, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Yimou Lin
- Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- National Health Commission (NHC) Key Laboratory of Combined Multi-Organ Transplantation, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Qi Ling
- Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- National Health Commission (NHC) Key Laboratory of Combined Multi-Organ Transplantation, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
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10
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Jin X, Zhang K, Fang T, Zeng X, Yan X, Tang J, Liang Z, Xie L, Zhao D. Low-dose PD-1 inhibitor combined with lenvatinib for preemptive treatment of recurrence after liver transplantation for hepatocellular carcinoma: Case report and literature review. Front Oncol 2022; 12:951303. [PMID: 36119543 PMCID: PMC9478730 DOI: 10.3389/fonc.2022.951303] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 08/10/2022] [Indexed: 11/18/2022] Open
Abstract
Orthotopic liver transplantation (OLT), as one of the curative methods for the treatment of hepatocellular carcinoma (HCC), has brought hope to patients with HCC. However, treatment options for HCC recurrence and metastasis after liver transplantation are limited. Immune checkpoint inhibitor (ICI), such as programmed cell death protein 1 (PD-1) inhibitor, have been successfully used in advanced or metastatic HCC, but the data on the safety of PD-1 inhibitor after liver transplantation is limited. In this article, we report a 47-year-old patient with acute-on-chronic liver failure and multiple HCC who was successfully treated with liver transplantation. On the 45th day after OLT, the patient’s alpha fetoprotein (AFP) and lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) were increased, and imaging examination showed no residual tumor. The patient had high risk factors for tumor recurrence before operation, so the possibility of tumor recurrence was considered. When the tumor markers showed an upward trend, we immediately treated the patient with lenvatinib 8 mg, after half a month, the AFP and AFP-L3 continued to increase compared with before. Then we used low-dose nivolumab 40mg, the patient’s AFP and AFP-L3 gradually decreased. One month later, a second low-dose nivolumab 40mg was given, and the patient’s tumor markers gradually decreased to normal. No acute rejection and other complications occurred during the treatment. So far, we have followed up this patient for 2 years, and no tumor recurrence was observed. To our knowledge, this is the first reported case using a low dose of nivolumab in combination with lenvatinib to prevent recurrence of HCC after liver transplantation.
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11
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Kawashima S, Joachim K, Abdelrahim M, Abudayyeh A, Jhaveri KD, Murakami N. Immune checkpoint inhibitors for solid organ transplant recipients: clinical updates. KOREAN JOURNAL OF TRANSPLANTATION 2022; 36:82-98. [PMID: 35919193 PMCID: PMC9296977 DOI: 10.4285/kjt.22.0013] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 04/21/2022] [Accepted: 04/26/2022] [Indexed: 11/22/2022] Open
Abstract
Transplant care continues to advance with increasing clinical experience and improvements in immunosuppressive therapy. As the population ages and long-term survival improves, transplant patient care has become more complex due to comorbidities, frailty, and the increased prevalence of cancer posttransplantation. Immune checkpoint inhibitors (ICIs) have become a standard treatment option for many cancers in non-transplant patients, but the use of ICIs in transplant patients is challenging due to the possibility of disrupting immune tolerance. However, over the past few years, ICIs have gradually started to be used in transplant patients as well. In this study, we review the current use of ICIs after all solid organ transplantation procedures (kidney, liver, heart, and lung). Increasing data suggest that the type and number of immunosuppressants may affect the risk of rejection after immunotherapy. Immunotherapy for cancer in transplant patients may be a feasible option for selected patients; however, prospective trials in specific organ transplant recipients are needed.
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Affiliation(s)
- Shun Kawashima
- Transplantation Research Center, Division of Renal Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Kole Joachim
- Transplantation Research Center, Division of Renal Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Maen Abdelrahim
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX, USA
| | - Ala Abudayyeh
- Section of Nephrology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Kenar D. Jhaveri
- Division of Kidney Diseases and Hypertension, Donald and Barbara Zucker School of Medicine at Hofstra/ Northwell, Great Neck, NY, USA
- Department of Internal Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USA
| | - Naoka Murakami
- Transplantation Research Center, Division of Renal Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
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12
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Xie M, Dang ZP, Sun XG, Zhang B, Zhang Q, Tian QJ, Cai JZ, Rao W. An analysis report on the application of immune checkpoint inhibitors after liver transplantation. Ther Adv Chronic Dis 2022; 13:20406223221099334. [PMID: 35620187 PMCID: PMC9127875 DOI: 10.1177/20406223221099334] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 04/21/2022] [Indexed: 01/05/2023] Open
Abstract
Up to now, a variety of immune checkpoint inhibitors (ICIs) have been proved to have good therapeutic effects in the treatment of hepatocellular carcinoma (HCC). However, the effects of their applications in liver transplant (LT) recipients are still unclear. In this analysis report, the clinical applications and therapeutic effects of ICIs on LT recipients with hepatic tumor recurrence or de novo carcinoma based on eight databases, including PubMed, EMBASE, Web of Science, Google Scholar, China National Knowledge Infrastructure, Wanfang Data, and CQVIP, were investigated. And the prior treatment, disease response, adverse reactions, and prognosis of patients with malignant tumors after LT and receiving ICI treatments were analyzed. After screening, a total of 28 articles with 47 recipients on the application of ICIs after LT were included. In these patients, their median age was 57 (14–71) years and the main type of tumor after LT was HCC (59.6%). The overall remission rate following ICI treatment was 29.8% (14/47) and the disease progression rate was 68.1% (32/47). Among all these patients, 31.9% (15/47) of patients had immune rejection; the median survival time was 6.5 (0.3–48) months, and the fatality rate was 61.7% (29/47). Considering that the therapeutic effect of ICIs in LT recipients with HCC recurrence or de novo carcinoma is not ideal, ICI treatment should be carefully considered for LT patients, and further research is needed.
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Affiliation(s)
- Man Xie
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Zhi-ping Dang
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xue-guo Sun
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Bei Zhang
- Department of Immunology, Medical College of Qingdao University, Qingdao, China
| | - Qun Zhang
- Division of Hepatology, Liver Disease Center, The Affiliated Hospital of Qingdao University, Qingdao, China
- Department of Organ Transplantation, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Qiu-ju Tian
- Division of Hepatology, Liver Disease Center, The Affiliated Hospital of Qingdao University, Qingdao, China
- Department of Organ Transplantation, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Jin-zhen Cai
- Division of Hepatology, Liver Disease Center, The Affiliated Hospital of Qingdao University, Qingdao, China
- Department of Organ Transplantation, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Wei Rao
- Division of Hepatology, Liver Disease Center, Department of Organ Transplantation, The Affiliated Hospital of Qingdao University, No. 59 Hai’er Road, Laoshan District, Qingdao City 266600, Shandong Province, China
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13
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Luo Y, Teng F, Fu H, Ding GS. Immunotherapy in liver transplantation for hepatocellular carcinoma: Pros and cons. World J Gastrointest Oncol 2022; 14:163-180. [PMID: 35116109 PMCID: PMC8790424 DOI: 10.4251/wjgo.v14.i1.163] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 06/30/2021] [Accepted: 12/08/2021] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation (LT) has emerged as a curative strategy for hepatocellular carcinoma (HCC), but contributes to a higher predisposition to HCC recurrence in the immunosuppression context, especially for tumors beyond the Milan criteria. Although immunotherapy has dramatically improved survival for immunocompetent patients and has become the standard of care for a variety of tumors, including HCC, it is mainly used outside the scope of organ transplantation owing to potentially fatal allograft rejection. Nevertheless, accumulative evidence has expanded the therapeutic paradigms of immunotherapy for HCC, from downstaging or bridging management in the pretransplant setting to the salvage or adjuvant strategy in the posttransplant setting. Generally, immunotherapy mainly includes immune checkpoint inhibitors (ICIs), adoptive cell transfer (ACT) and vaccine therapy. ICIs, followed by ACT, have been most investigated in LT, with some promising results. Because of the complex tumor microenvironment and immunoreactivity when immunosuppressants are combined with immunotherapy, it is difficult to reach formulations for immunosuppressant adjustment and the optimal selection of immunotherapy as well as patients. In addition, the absence of effective biomarkers for identifying rejection and tumor response is still an unresolved barrier to successful clinical immunotherapy applications for LT. In this review, we comprehensively summarize the available evidence of immunotherapy used in LT that is specific to HCC. Moreover, we discuss clinically concerning issues regarding the concurrent goals of graft protection and antitumor response.
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Affiliation(s)
- Yi Luo
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
| | - Fei Teng
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
| | - Hong Fu
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
| | - Guo-Shan Ding
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
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14
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Ao H, Xin Z, Jian Z. Liquid biopsy to identify biomarkers for immunotherapy in hepatocellular carcinoma. Biomark Res 2021; 9:91. [PMID: 34930486 PMCID: PMC8686238 DOI: 10.1186/s40364-021-00348-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 11/03/2021] [Indexed: 12/12/2022] Open
Abstract
The past years have witnessed the vigorous development of immunotherapy, mainly immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1) protein and its ligand, PD-L1, and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). Indeed, ICIs have largely revolutionized the management and improved the prognosis of patients with intermediate and advanced hepatocellular carcinoma (HCC). However, biomarker-based stratification of HCC patients for optimal response to ICI treatment is still of unmet need and again, there exists the necessity to dynamically monitor treatment effect in real-time manner. The role of conventional biomarkers in immunotherapy surveillance is largely limited by spatial and temporal tumor heterogeneity whereas liquid biopsy seems to be promising to circumvent tumor heterogeneity to identify candidate patients who may response to immunotherapy, to dynamically monitor treatment effect and to unveil resistance mechanism. Herein, we provide a thorough review about the potential utility of liquid biopsy in immunotherapy for HCC and discuss its future perspectives.
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Affiliation(s)
- Huang Ao
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education; Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Zhang Xin
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education; Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Zhou Jian
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education; Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
- Institute of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
- State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China.
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, China.
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