Immune checkpoint therapy in liver cancer
DOI:
https://doi.org/10.54097/6xxj3f63Keywords:
Immune checkpoint, hepatocellular carcinoma, immunotherapy.Abstract
Immune checkpoint therapies have been shown to be extremely successful in the treatment of cancer, with clinical utilization already established for suppressing CTLA-4, PD-1, and PD-L1. The CTLA-4 antibody ipilimumab and the PD-1 antibody pembrolizumab were demonstrated to improve survival in patients with metastatic melanoma. The Food and Drug Administration (FDA) has given approval to certain matching medications for the medical care of various tumors based on these targets. The current study also confirms the potential of these immune checkpoints and inhibitors to treat hepatocellular carcinoma. The objective of ongoing research is to integrate immune checkpoint therapy into hepatocellular carcinoma management, either as a standalone treatment or in combination with other therapeutic modalities, to enhance patient outcomes and survival. In this review, the specific roles and mechanisms of immune checkpoints and inhibitors in hepatocellular carcinoma are presented, as well as summarizing the current progress in their therapeutic use in the treatment of HCC and discussing their directions.
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References
Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA: A Cancer Journal for Clinicians, 2023, 73 (1): 17 – 48.
Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, et al. Hepatocellular carcinoma. Nature Reviews Disease Primers, 2021, 7 (1): 6.
Sangro B, Gomez-Martin C, de la Mata M, Iñarrairaegui M, Garralda E, Barrera P, et al. A clinical trial of CTLA-4 blockades with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C. Journal of Hepatology, 2013, 59 (1): 81 – 8.
Duffy AG, Ulahannan SV, Makorova-Rusher O, Rahma O, Wedemeyer H, Pratt D, et al. Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma. Journal of Hepatology, 2017, 66 (3): 545 – 51.
El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. The Lancet, 2017, 389 (10088): 2492 – 502.
Yau T, Kang YK, Kim TY, El-Khoueiry AB, Santoro A, Sangro B, et al. Efficacy and Safety of Nivolumab Plus Ipilimumab in Patients with Advanced Hepatocellular Carcinoma Previously Treated with Sorafenib: The CheckMate 040 Randomized Clinical Trial. JAMA Oncology, 2020, 6 (11): e204564 – e204564.
Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer D, et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. The Lancet Oncology, 2018, 19 (7): 940 – 52.
Zheng Y, Wang S, Cai J, Ke A, Fan J. The progress of immune checkpoint therapy in primary liver cancer. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 2021, 1876 (2): 188638.
Gordon SR, Maute RL, Dulken BW, Hutter G, George BM, McCracken MN, Gupta R, Tsai JM, Sinha R, Corey D, Ring AM, Connolly AJ, Weissman IL. PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature, 2017, 545 (7655): 495 - 499.
Wu K, Kryczek I, Chen L, Zou W, Welling TH. Kupffer cell suppression of CD8+ T cells in human hepatocellular carcinoma is mediated by B7-H1/programmed death-1 interactions. Cancer Res, 2009, 69 (20): 8067 - 75.
Xu F, Jin T, Zhu Y, Dai C. Immune checkpoint therapy in liver cancer. J Exp Clin Cancer Res, 2018, 37 (1): 110.
Wang J, Li J, Tang G, Tian Y, Su S, Li Y. Clinical outcomes and influencing factors of PD-1/PD-L1 in hepatocellular carcinoma. Oncol Lett, 2021, 21 (4): 279.
Yau T, Park JW, Finn RS, et al. LBA38_PR - CheckMate 459: A randomized, multi-center phase III study of nivolumab (NIVO) vs sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC). Annals of Oncology, 2019, 30: v874 - v875.
Finn RS, Ryoo BY, Merle P, et al. Pembrolizumab as Second-Line Therapy in Patients with Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial. JCO, 2020, 38 (3): 193 - 202.
Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med, 2020, 382 (20): 1894 - 1905.
Kelley RK, Sangro B, Harris W, et al. Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients with Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study. J Clin Oncol, 2021, 39 (27): 2991 - 3001.
Sharma P, Goswami S, Raychaudhuri D, Siddiqui BA, Singh P, Nagarajan A, et al. Immune checkpoint therapy—current perspectives and future directions. Cell, 2023, 186 (8): 1652 – 69.
Hosseini A, Gharibi T, Marofi F, Babaloo Z, Baradaran B. CTLA-4: From mechanism to autoimmune therapy. International Immunopharmacology, 2020, 80: 106221.
Graziani G, Tentori L, Navarra P. Ipilimumab: A novel immunostimulatory monoclonal antibody for the treatment of cancer. Pharmacological Research, 2012, 65 (1): 9 – 22.
Yau T, Kang YK, Kim TY, et al. Efficacy and Safety of Nivolumab Plus Ipilimumab in Patients with Advanced Hepatocellular Carcinoma Previously Treated with Sorafenib: The CheckMate 040 Randomized Clinical Trial. JAMA Oncology, 2020, 6 (11): e204564 - e204564.
Zhou G, Sprengers D, Boor PPC, et al. Antibodies Against Immune Checkpoint Molecules Restore Functions of Tumor-Infiltrating T Cells in Hepatocellular Carcinomas. Gastroenterology, 2017, 153 (4): 1107 - 1119.e10.
Wierz M, Pierson S, Guyonnet L, Viry E, Lequeux A, Oudin A, et al. Dual PD1/LAG3 immune checkpoint blockade limits tumor development in a murine model of chronic lymphocytic leukemia. Blood, 2018, 131 (14): 1617 – 21.
Tawbi HA, Schadendorf D, Lipson EJ, et al. Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma. N Engl J Med, 2022, 386 (1): 24 - 34.
Schöffski P, Tan DSW, Martín M, et al. Phase I/II study of the LAG-3 inhibitor ieramilimab (LAG525) ± anti-PD-1 spartalizumab (PDR001) in patients with advanced malignancies. J Immunother Cancer, 2022, 10 (2): e003776.
Cai L, Li Y, Tan J, Xu L, Li Y. Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy. Journal of Hematology & Oncology, 2023, 16 (1): 101.
Li Z, Li N, Li F, et al. Immune checkpoint proteins PD-1 and TIM-3 are both highly expressed in liver tissues and correlate with their gene polymorphisms in patients with HBV-related hepatocellular carcinoma. Medicine (Baltimore), 2016, 95 (52): e5749.
Curigliano G, Gelderblom H, Mach N, et al. Phase I/Ib Clinical Trial of Sabatolimab, an Anti-TIM-3 Antibody, Alone and in Combination with Spartalizumab, an Anti-PD-1 Antibody, in Advanced Solid Tumors. Clin Cancer Res, 2021, 27 (13): 3620 - 3629.
Liu Z, Lin Y, Zhang J, et al. Molecular targeted and immune checkpoint therapy for advanced hepatocellular carcinoma. Journal of Experimental & Clinical Cancer Research, 2019, 38 (1): 447.
Huang Y, Zhang Y, Zhang M, Zhao K, Feng L, Guan J, et al. Combined immunotherapy for hepatocellular carcinoma: How to maximize immune checkpoint blockade synergic anti-tumor effect. Critical Reviews in Oncology/Hematology, 2023, 189: 104070.
Ikeda K, Kudo M, Kawazoe S, et al. Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma. J Gastroenterol, 2017, 52 (4):512 - 519.
Llovet JM, Vogel A, Madoff DC, et al. Randomized Phase 3 LEAP-012 Study: Transarterial Chemoembolization with or Without Lenvatinib Plus Pembrolizumab for Intermediate-Stage Hepatocellular Carcinoma Not Amenable to Curative Treatment. Cardiovasc Intervent Radiol, 2022, 45 (4): 405 - 412.
Kelley RK, Verslype C, Cohn AL, et al. Cabozantinib in hepatocellular carcinoma: results of a phase 2 placebo-controlled randomized discontinuation study. Ann Oncol, 2017, 28 (3): 528 - 534.
Cammarota A, Zanuso V, D’Alessio A, Pressiani T, Personeni N, Rimassa L. Cabozantinib plus atezolizumab for the treatment of advanced hepatocellular carcinoma: Shedding light on the preclinical rationale and clinical trials. Expert Opinion on Investigational Drugs, 2022, 31.
Zhu L, Lei Y, Huang J, et al. Recent advances in oncolytic virus therapy for hepatocellular carcinoma. Frontiers in Oncology, 2023, 13.
Zhang Y, Zhang H, Wei M, et al. Recombinant Adenovirus Expressing a Soluble Fusion Protein PD-1/CD137L Subverts the Suppression of CD8+ T Cells in HCC. Mol Ther, 2019, 27 (11): 1906 - 1918.
Sanmamed MF, Berraondo P, Rodriguez-Ruiz ME, Melero I. Charting roadmaps towards novel and safe synergistic immunotherapy combinations. Nat Cancer, 2022, 3 (6): 665 - 680.
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