2024 08 v.59 1295-1301
肝癌免疫治疗的挑战与机遇
基金项目(Foundation):
安徽省临床医学研究转化专项(编号：2022042951070 20008);;
安徽省高校科研项目(编号：2022AH010070)
邮箱(Email):
sunbc@ahmu.edu.cn;
DOI:
10.19405/j.cnki.issn1000-1492.2024.08.001
中文作者单位:
安徽医科大学第一附属医院肝胆胰及移植外科;
摘要(Abstract):
肝癌在全球范围内是第六大最常见的癌症类型，同时也是导致癌症死亡的第三大原因。约有30%的患者在诊断时处于肝癌早期阶段，此时可以通过包括肝部分切除术和肝移植在内的治愈性治疗手段进行治疗，使得患者的中位总生存期能够超过60个月。然而，大多数患者在被确诊时已进展至肝癌晚期，此时的治疗选项常可采用靶向治疗和免疫检查点抑制剂。尤其是包含免疫检查点抑制剂的系统性治疗，在显著改善晚期肝癌患者的预后方面可发挥重要作用。因此，深入探索肝癌的免疫微环境特征，积极识别免疫治疗的生物标志物，对于推进和完善肝癌免疫治疗至关重要。
关键词(KeyWords):
肝癌;;免疫微环境;;生物标志物;;免疫治疗
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参考文献
[1] Llovet J M,Kelley R K,Villanueva A,et al.Hepatocellular carcinoma[J].Nat Rev Dis Primers,2021,7(1):6.
[2] Llovet J M,Pinyol R,Kelley R K,et al.Molecular pathogenesis and systemic therapies for hepatocellular carcinoma[J].Nat Cancer,2022,3(4):386-401.
[3] Finn R S,Qin S,Ikeda M,et al.Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma[J].N Engl J Med,2020,382(20):1894-905.
[4] Cappuyns S,Corbett V,Yarchoan M,et al.Critical appraisal of guideline recommendations on systemic therapies for advanced hepatocellular carcinoma:a review[J].JAMA Oncol,2024,10(3):395-404.
[5] Singal A G,Llovet J M,Yarchoan M,et al.AASLD practice guidance on prevention,diagnosis,and treatment of hepatocellular carcinoma[J].Hepatology,2023,78(6):1922-65.
[6] Hanahan D,Weinberg R A.The hallmarks of cancer[J].Cell,2000,100(1):57-70.
[7] Hanahan D,Weinberg R A.Hallmarks of cancer:the next generation[J].Cell,2011,144(5):646-74.
[8] Hanahan D.Hallmarks of cancer:new dimensions[J].Cancer Discov,2022,12(1):31-46.
[9] Yuan S,Almagro J,Fuchs E.Beyond genetics:driving cancer with the tumour microenvironment behind the wheel[J].Nat Rev Cancer,2024,24(4):274-86.
[10] Llovet J M,Castet F,Heikenwalder M,et al.Immunotherapies for hepatocellular carcinoma[J].Nat Rev Clin Oncol,2022,19(3):151-72.
[11] Chen J,Feng W,Sun M,et al.TGF-beta1-induced SOX18 elevation promotes hepatocellular carcinoma progression and metastasis through transcriptionally upregulating PD-L1 and CXCL12[J].Gastroenterology,2024,167(2):264-80.
[12] Zhang W,Zhangyuan G,Wang F,et al.The zinc finger protein Miz1 suppresses liver tumorigenesis by restricting hepatocyte-driven macrophage activation and inflammation[J].Immunity,2021,54(6):1168-85.e8.
[13] Lin J,Rao D,Zhang M,et al.Metabolic reprogramming in the tumor microenvironment of liver cancer[J].J Hematol Oncol,2024,17(1):6.
[14] Ringelhan M,Pfister D,O′Connor T,et al.The immunology of hepatocellular carcinoma[J].Nat Immunol,2018,19(3):222-32.
[15] Yang J D,Nakamura I,Roberts L R.The tumor microenvironment in hepatocellular carcinoma:current status and therapeutic targets[J].Semin Cancer Bio,2011,21(1):35-43.
[16] Wculek S K,Cueto F J,Mujal A M,et al.Dendritic cells in cancer immunology and immunotherapy[J].Nat Rev Immunol,2020,20(1):7-24.
[17] de Galarreta M R,Bresnahan E,Molina-Sánchez P,et al.beta-Catenin activation promotes immune escape and resistance to anti-PD-1 therapy in hepatocellular Carcinoma[J].Cancer Discov,2019,9(8):1124-41.
[18] Nishida N.Role of oncogenic pathways on the cancer immunosuppressive microenvironment and its clinical implications in hepatocellular carcinoma[J].Cancers (Basel),2021,13(15):3666.
[19] Tang F,Li J,Qi L,et al.A pan-cancer single-cell panorama of human natural killer cells[J].Cell,2023,186(19):4235-51.e20.
[20] Zhou Y,Cheng L,Liu L,et al.NK cells are never alone:crosstalk and communication in tumour microenvironments[J].Mol Cancer,2023,22(1):34.
[21] Lazarova M,Steinle A.Impairment of NKG2D-Mediated Tumor Immunity by TGF-beta[J].Front Immunol,2019,10:2689.
[22] Arai J,Goto K,Tanoue Y,et al.Enzymatic inhibition of MICA sheddase ADAM17 by lomofungin in hepatocellular carcinoma cells[J].Int J Cancer,2018,143(10):2575-83.
[23] Wu Y,Kuang D M,Pan W D,et al.Monocyte/macrophage-elicited natural killer cell dysfunction in hepatocellular carcinoma is mediated by CD48/2B4 interactions[J].Hepatology,2013,57(3):1107-16.
[24] Tan J,Fan W,Liu T,et al.TREM2(+) macrophages suppress CD8(+) T-cell infiltration after transarterial chemoembolisation in hepatocellular carcinoma[J].J Hepatol,2023,79(1):126-40.
[25] Cai N,Cheng K,Ma Y,et al.Targeting MMP9 in CTNNB1 mutant hepatocellular carcinoma restores CD8(+) T cell-mediated antitumour immunity and improves anti-PD-1 efficacy[J].Gut,2024,73(6):985-99.
[26] Motz G T,Santoro S P,Wang L P,et al.Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors[J].Nat Med,2014,20(6):607-15.
[27] Baessler A,Vignali D A A.T cell exhaustion[J].Annu Rev Immunol,2024,42(1):179-206.
[28] Scott A C,Dündar F,Zumbo P,et al.TOX is a critical regulator of tumour-specific T cell differentiation[J].Nature,2019,571(7764):270-4.
[29] Wang X,He Q,Shen H,et al.TOX promotes the exhaustion of antitumor CD8(+) T cells by preventing PD1 degradation in hepatocellular carcinoma[J].J Hepatol,2019,71(4):731-41.
[30] Huang Q,Wu X,Wang Z,et al.The primordial differentiation of tumor-specific memory CD8(+) T cells as bona fide responders to PD-1/PD-L1 blockade in draining lymph nodes[J].Cell,2022,185(22):4049-66.e25.
[31] Prieto J,Melero I,Sangro B.Immunological landscape and immunotherapy of hepatocellular carcinoma[J].Nat Rev Gastroenterol Hepatol,2015,12(12):681-700.
[32] Chen Q,Sun T,Jiang C.Recent advancements in nanomedicine for ′cold′ tumor immunotherapy[J].Nanomicro Lett,2021,13(1):92.
[33] Delire B,Henriet P,Lemoine P,et al.Chronic liver injury promotes hepatocarcinoma cell seeding and growth,associated with infiltration by macrophages[J].Cancer Sci,2018,109(7):2141-52.
[34] Arvanitakis K,Koletsa T,Mitroulis I,et al.Tumor-associated macrophages in hepatocellular carcinoma pathogenesis,prognosis and therapy[J].Cancers (Basel),2022,14(1):226.
[35] O′Rourke J M,Patten D A,Shetty S.Tumour-associated macrophages in hepatocellular carcinoma:Pressing the metabolic switch to prevent T cell responses[J].J Hepatol,2019,71(2):243-5.
[36] Zheng C,Zheng L,Yoo J K,et al.Landscape of infiltrating T cells in liver cancer revealed by single-cell sequencing[J].Cell,2017,169(7):1342-56.e16.
[37] Park D J,Sung P S,Lee G W,et al.Preferential expression of programmed death ligand 1 protein in tumor-associated macrophages and its potential role in immunotherapy for hepatocellular carcinoma[J].Int J Mol Sci,2021,22(9):4710.
[38] Zhang W,Liu Y,Yan Z,et al.IL-6 promotes PD-L1 expression in monocytes and macrophages by decreasing protein tyrosine phosphatase receptor type O expression in human hepatocellular carcinoma[J].J Immunother Cancer,2020,8(1):e000285.
[39] Liu J,Fan L,Yu H,et al.Endoplasmic reticulum stress causes liver cancer cells to release exosomal miR-23a-3p and up-regulate programmed death ligand 1 expression in macrophages[J].Hepatology,2019,70(1):241-58.
[40] Zhang Q,He Y,Luo N,et al.Landscape and dynamics of single immune cells in hepatocellular carcinoma[J].Cell,2019,179(4):829-45.e20.
[41] Geh D,Leslie J,Rumney R,et al.Neutrophils as potential therapeutic targets in hepatocellular carcinoma[J].Nat Rev Gastroenterol Hepatol,2022,19(4):257-73.
[42] Hoechst B,Ormandy L A,Ballmaier M,et al.A new population of myeloid-derived suppressor cells in hepatocellular carcinoma patients induces CD4(+)CD25(+)Foxp3(+) T cells[J].Gastroenterology,2008,135(1):234-43.
[43] Pallett L J,Gill U S,Quaglia A,et al.Metabolic regulation of hepatitis B immunopathology by myeloid-derived suppressor cells[J].Nat Med,2015,21(6):591-600.
[44] Rodríguez P C,Ochoa A C.Arginine regulation by myeloid derived suppressor cells and tolerance in cancer:mechanisms and therapeutic perspectives[J].Immunol Rev,2008,222:180-91.
[45] Wang N,Tan H Y,Lu Y,et al.PIWIL1 governs the crosstalk of cancer cell metabolism and immunosuppressive microenvironment in hepatocellular carcinoma[J].Signal Transduct Target Ther,2021,6(1):86.
[46] Ohl K,Tenbrock K.Reactive oxygen species as regulators of MDSC-mediated immune suppression[J].Front Immunol,2018,9:2499.
[47] Wang Y,Zhang T,Sun M,et al.Therapeutic values of myeloid-derived suppressor cells in hepatocellular carcinoma:facts and hopes[J].Cancers (Basel),2021,13(20):5127.
[48] Harkus U,Wankell M,Palamuthusingam P,et al.Immune checkpoint inhibitors in HCC:cellular,molecular and systemic data[J].Semin Cancer Biol,2022,86(Pt 3):799-815.
[49] Pinato D J,Guerra N,Fessas P,et al.Immune-based therapies for hepatocellular carcinoma[J].Oncogene,2020,39(18):3620-37.
[50] Yu S J,Greten T F.Deciphering and reversing immunosuppressive cells in the treatment of hepatocellular carcinoma[J].J Liver Cancer,2020,20(1):1-16.
[51] Ruf B,Heinrich B,Greten T F.Immunobiology and immunotherapy of HCC:spotlight on innate and innate-like immune cells[J].Cell Mol Immunol,2021,18(1):112-27.
[52] Finkin S,Yuan D,Stein I,et al.Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma[J].Nat Immunol,2015,16(12):1235-44.
[53] Shao Y,Lo C M,Ling C C,et al.Regulatory B cells accelerate hepatocellular carcinoma progression via CD40/CD154 signaling pathway[J].Cancer Lett,2014,355(2):264-72.
[54] Sarvaria A,Madrigal J A,Saudemont A.B cell regulation in cancer and anti-tumor immunity[J].Cell Mol Immunol,2017,14(8):662-74.
[55] Brown Z J,Tsilimigras D I,Ruff S M,et al.Management of hepatocellular carcinoma:a review[J].JAMA Surg,2023,158(4):410-20.
[56] Llovet J M,De Baere T,Kulik L,et al.Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma[J].Nat Rev Gastroenterol Hepatol,2021,18(5):293-313.
[57] Abou-Alfa G K,Lau G,Kudo M,et al.Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma[J].NEJM Evid,2022,1(8):EVIDoa2100070.
[58] El-Khoueiry A B,Sangro B,Yau T,et al.Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040):an open-label,non-comparative,phase 1/2 dose escalation and expansion trial[J].Lancet,2017,389(10088):2492-502.
[59] El-Khoueiry A B,Trojan J,Meyer T,et al.Nivolumab in sorafenib-naive and sorafenib-experienced patients with advanced hepatocellular carcinoma:5-year follow-up from CheckMate 040[J].Ann Oncol,2024,35(4):381-91.
[60] Zhu A X,Finn R S,Edeline J,et al.Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224):a non-randomised,open-label phase 2 trial[J].Lancet Oncol,2018,19(7):940-52.
[61] Kudo M,Finn R S,Edeline J,et al.Updated efficacy and safety of KEYNOTE-224:a phase II study of pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib[J].Eur J Cancer,2022,167:1-12.
[62] Finn R S,Ryoo B Y,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[J].J Clin Oncol,2020,38(3):193-202.
[63] Merle P,Kudo M,Edeline J,et al.Pembrolizumab as second-line therapy for advanced hepatocellular carcinoma:longer term follow-up from the phase 3 KEYNOTE-240 trial[J].Liver Cancer,2023,12(4):309-20.
[64] Yau T,Kang Y K,Kim T Y,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[J].JAMA Oncol,2020,6(11):e204564.
[65] Gao X,Xu N,Li Z,et al.Safety and antitumour activity of cadonilimab,an anti-PD-1/CTLA-4 bispecific antibody,for patients with advanced solid tumours (COMPASSION-03):a multicentre,open-label,phase 1b/2 trial[J].Lancet Oncol,2023,24(10):1134-46.
[66] Zhu H D,Li H L,Huang M S,et al.Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001)[J].Signal Transduct Target Ther,2023,8(1):58.
[67] Xu J,Shen J,Gu S,et al.Camrelizumab in combination with apatinib in patients with advanced hepatocellular carcinoma (RESCUE):a nonrandomized,open-label,phase II trial[J].Clin Cancer Res,2021,27(4):1003-11.
[68] Qin S,Chan S L,Gu S,et al.Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310):a randomised,open-label,international phase 3 study[J].Lancet,2023,402(10408):1133-46.
[69] Kelley R K,Rimassa L,Cheng A L,et al.Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312):a multicentre,open-label,randomised,phase 3 trial[J].Lancet Oncol,2022,23(8):995-1008.
[70] Cheng A L,Qin S,Ikeda M,et al.Updated efficacy and safety data from IMbrave150:Atezolizumab plus bevacizumab vs.sorafenib for unresectable hepatocellular carcinoma[J].J Hepatol,2022,76(4):862-73.
[71] Ren Z,Xu J,Bai Y,et al.Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32):a randomised,open-label,phase 2-3 study[J].Lancet Oncol,2021,22(7):977-90.
[2] Llovet J M,Pinyol R,Kelley R K,et al.Molecular pathogenesis and systemic therapies for hepatocellular carcinoma[J].Nat Cancer,2022,3(4):386-401.
[3] Finn R S,Qin S,Ikeda M,et al.Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma[J].N Engl J Med,2020,382(20):1894-905.
[4] Cappuyns S,Corbett V,Yarchoan M,et al.Critical appraisal of guideline recommendations on systemic therapies for advanced hepatocellular carcinoma:a review[J].JAMA Oncol,2024,10(3):395-404.
[5] Singal A G,Llovet J M,Yarchoan M,et al.AASLD practice guidance on prevention,diagnosis,and treatment of hepatocellular carcinoma[J].Hepatology,2023,78(6):1922-65.
[6] Hanahan D,Weinberg R A.The hallmarks of cancer[J].Cell,2000,100(1):57-70.
[7] Hanahan D,Weinberg R A.Hallmarks of cancer:the next generation[J].Cell,2011,144(5):646-74.
[8] Hanahan D.Hallmarks of cancer:new dimensions[J].Cancer Discov,2022,12(1):31-46.
[9] Yuan S,Almagro J,Fuchs E.Beyond genetics:driving cancer with the tumour microenvironment behind the wheel[J].Nat Rev Cancer,2024,24(4):274-86.
[10] Llovet J M,Castet F,Heikenwalder M,et al.Immunotherapies for hepatocellular carcinoma[J].Nat Rev Clin Oncol,2022,19(3):151-72.
[11] Chen J,Feng W,Sun M,et al.TGF-beta1-induced SOX18 elevation promotes hepatocellular carcinoma progression and metastasis through transcriptionally upregulating PD-L1 and CXCL12[J].Gastroenterology,2024,167(2):264-80.
[12] Zhang W,Zhangyuan G,Wang F,et al.The zinc finger protein Miz1 suppresses liver tumorigenesis by restricting hepatocyte-driven macrophage activation and inflammation[J].Immunity,2021,54(6):1168-85.e8.
[13] Lin J,Rao D,Zhang M,et al.Metabolic reprogramming in the tumor microenvironment of liver cancer[J].J Hematol Oncol,2024,17(1):6.
[14] Ringelhan M,Pfister D,O′Connor T,et al.The immunology of hepatocellular carcinoma[J].Nat Immunol,2018,19(3):222-32.
[15] Yang J D,Nakamura I,Roberts L R.The tumor microenvironment in hepatocellular carcinoma:current status and therapeutic targets[J].Semin Cancer Bio,2011,21(1):35-43.
[16] Wculek S K,Cueto F J,Mujal A M,et al.Dendritic cells in cancer immunology and immunotherapy[J].Nat Rev Immunol,2020,20(1):7-24.
[17] de Galarreta M R,Bresnahan E,Molina-Sánchez P,et al.beta-Catenin activation promotes immune escape and resistance to anti-PD-1 therapy in hepatocellular Carcinoma[J].Cancer Discov,2019,9(8):1124-41.
[18] Nishida N.Role of oncogenic pathways on the cancer immunosuppressive microenvironment and its clinical implications in hepatocellular carcinoma[J].Cancers (Basel),2021,13(15):3666.
[19] Tang F,Li J,Qi L,et al.A pan-cancer single-cell panorama of human natural killer cells[J].Cell,2023,186(19):4235-51.e20.
[20] Zhou Y,Cheng L,Liu L,et al.NK cells are never alone:crosstalk and communication in tumour microenvironments[J].Mol Cancer,2023,22(1):34.
[21] Lazarova M,Steinle A.Impairment of NKG2D-Mediated Tumor Immunity by TGF-beta[J].Front Immunol,2019,10:2689.
[22] Arai J,Goto K,Tanoue Y,et al.Enzymatic inhibition of MICA sheddase ADAM17 by lomofungin in hepatocellular carcinoma cells[J].Int J Cancer,2018,143(10):2575-83.
[23] Wu Y,Kuang D M,Pan W D,et al.Monocyte/macrophage-elicited natural killer cell dysfunction in hepatocellular carcinoma is mediated by CD48/2B4 interactions[J].Hepatology,2013,57(3):1107-16.
[24] Tan J,Fan W,Liu T,et al.TREM2(+) macrophages suppress CD8(+) T-cell infiltration after transarterial chemoembolisation in hepatocellular carcinoma[J].J Hepatol,2023,79(1):126-40.
[25] Cai N,Cheng K,Ma Y,et al.Targeting MMP9 in CTNNB1 mutant hepatocellular carcinoma restores CD8(+) T cell-mediated antitumour immunity and improves anti-PD-1 efficacy[J].Gut,2024,73(6):985-99.
[26] Motz G T,Santoro S P,Wang L P,et al.Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors[J].Nat Med,2014,20(6):607-15.
[27] Baessler A,Vignali D A A.T cell exhaustion[J].Annu Rev Immunol,2024,42(1):179-206.
[28] Scott A C,Dündar F,Zumbo P,et al.TOX is a critical regulator of tumour-specific T cell differentiation[J].Nature,2019,571(7764):270-4.
[29] Wang X,He Q,Shen H,et al.TOX promotes the exhaustion of antitumor CD8(+) T cells by preventing PD1 degradation in hepatocellular carcinoma[J].J Hepatol,2019,71(4):731-41.
[30] Huang Q,Wu X,Wang Z,et al.The primordial differentiation of tumor-specific memory CD8(+) T cells as bona fide responders to PD-1/PD-L1 blockade in draining lymph nodes[J].Cell,2022,185(22):4049-66.e25.
[31] Prieto J,Melero I,Sangro B.Immunological landscape and immunotherapy of hepatocellular carcinoma[J].Nat Rev Gastroenterol Hepatol,2015,12(12):681-700.
[32] Chen Q,Sun T,Jiang C.Recent advancements in nanomedicine for ′cold′ tumor immunotherapy[J].Nanomicro Lett,2021,13(1):92.
[33] Delire B,Henriet P,Lemoine P,et al.Chronic liver injury promotes hepatocarcinoma cell seeding and growth,associated with infiltration by macrophages[J].Cancer Sci,2018,109(7):2141-52.
[34] Arvanitakis K,Koletsa T,Mitroulis I,et al.Tumor-associated macrophages in hepatocellular carcinoma pathogenesis,prognosis and therapy[J].Cancers (Basel),2022,14(1):226.
[35] O′Rourke J M,Patten D A,Shetty S.Tumour-associated macrophages in hepatocellular carcinoma:Pressing the metabolic switch to prevent T cell responses[J].J Hepatol,2019,71(2):243-5.
[36] Zheng C,Zheng L,Yoo J K,et al.Landscape of infiltrating T cells in liver cancer revealed by single-cell sequencing[J].Cell,2017,169(7):1342-56.e16.
[37] Park D J,Sung P S,Lee G W,et al.Preferential expression of programmed death ligand 1 protein in tumor-associated macrophages and its potential role in immunotherapy for hepatocellular carcinoma[J].Int J Mol Sci,2021,22(9):4710.
[38] Zhang W,Liu Y,Yan Z,et al.IL-6 promotes PD-L1 expression in monocytes and macrophages by decreasing protein tyrosine phosphatase receptor type O expression in human hepatocellular carcinoma[J].J Immunother Cancer,2020,8(1):e000285.
[39] Liu J,Fan L,Yu H,et al.Endoplasmic reticulum stress causes liver cancer cells to release exosomal miR-23a-3p and up-regulate programmed death ligand 1 expression in macrophages[J].Hepatology,2019,70(1):241-58.
[40] Zhang Q,He Y,Luo N,et al.Landscape and dynamics of single immune cells in hepatocellular carcinoma[J].Cell,2019,179(4):829-45.e20.
[41] Geh D,Leslie J,Rumney R,et al.Neutrophils as potential therapeutic targets in hepatocellular carcinoma[J].Nat Rev Gastroenterol Hepatol,2022,19(4):257-73.
[42] Hoechst B,Ormandy L A,Ballmaier M,et al.A new population of myeloid-derived suppressor cells in hepatocellular carcinoma patients induces CD4(+)CD25(+)Foxp3(+) T cells[J].Gastroenterology,2008,135(1):234-43.
[43] Pallett L J,Gill U S,Quaglia A,et al.Metabolic regulation of hepatitis B immunopathology by myeloid-derived suppressor cells[J].Nat Med,2015,21(6):591-600.
[44] Rodríguez P C,Ochoa A C.Arginine regulation by myeloid derived suppressor cells and tolerance in cancer:mechanisms and therapeutic perspectives[J].Immunol Rev,2008,222:180-91.
[45] Wang N,Tan H Y,Lu Y,et al.PIWIL1 governs the crosstalk of cancer cell metabolism and immunosuppressive microenvironment in hepatocellular carcinoma[J].Signal Transduct Target Ther,2021,6(1):86.
[46] Ohl K,Tenbrock K.Reactive oxygen species as regulators of MDSC-mediated immune suppression[J].Front Immunol,2018,9:2499.
[47] Wang Y,Zhang T,Sun M,et al.Therapeutic values of myeloid-derived suppressor cells in hepatocellular carcinoma:facts and hopes[J].Cancers (Basel),2021,13(20):5127.
[48] Harkus U,Wankell M,Palamuthusingam P,et al.Immune checkpoint inhibitors in HCC:cellular,molecular and systemic data[J].Semin Cancer Biol,2022,86(Pt 3):799-815.
[49] Pinato D J,Guerra N,Fessas P,et al.Immune-based therapies for hepatocellular carcinoma[J].Oncogene,2020,39(18):3620-37.
[50] Yu S J,Greten T F.Deciphering and reversing immunosuppressive cells in the treatment of hepatocellular carcinoma[J].J Liver Cancer,2020,20(1):1-16.
[51] Ruf B,Heinrich B,Greten T F.Immunobiology and immunotherapy of HCC:spotlight on innate and innate-like immune cells[J].Cell Mol Immunol,2021,18(1):112-27.
[52] Finkin S,Yuan D,Stein I,et al.Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma[J].Nat Immunol,2015,16(12):1235-44.
[53] Shao Y,Lo C M,Ling C C,et al.Regulatory B cells accelerate hepatocellular carcinoma progression via CD40/CD154 signaling pathway[J].Cancer Lett,2014,355(2):264-72.
[54] Sarvaria A,Madrigal J A,Saudemont A.B cell regulation in cancer and anti-tumor immunity[J].Cell Mol Immunol,2017,14(8):662-74.
[55] Brown Z J,Tsilimigras D I,Ruff S M,et al.Management of hepatocellular carcinoma:a review[J].JAMA Surg,2023,158(4):410-20.
[56] Llovet J M,De Baere T,Kulik L,et al.Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma[J].Nat Rev Gastroenterol Hepatol,2021,18(5):293-313.
[57] Abou-Alfa G K,Lau G,Kudo M,et al.Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma[J].NEJM Evid,2022,1(8):EVIDoa2100070.
[58] El-Khoueiry A B,Sangro B,Yau T,et al.Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040):an open-label,non-comparative,phase 1/2 dose escalation and expansion trial[J].Lancet,2017,389(10088):2492-502.
[59] El-Khoueiry A B,Trojan J,Meyer T,et al.Nivolumab in sorafenib-naive and sorafenib-experienced patients with advanced hepatocellular carcinoma:5-year follow-up from CheckMate 040[J].Ann Oncol,2024,35(4):381-91.
[60] Zhu A X,Finn R S,Edeline J,et al.Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224):a non-randomised,open-label phase 2 trial[J].Lancet Oncol,2018,19(7):940-52.
[61] Kudo M,Finn R S,Edeline J,et al.Updated efficacy and safety of KEYNOTE-224:a phase II study of pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib[J].Eur J Cancer,2022,167:1-12.
[62] Finn R S,Ryoo B Y,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[J].J Clin Oncol,2020,38(3):193-202.
[63] Merle P,Kudo M,Edeline J,et al.Pembrolizumab as second-line therapy for advanced hepatocellular carcinoma:longer term follow-up from the phase 3 KEYNOTE-240 trial[J].Liver Cancer,2023,12(4):309-20.
[64] Yau T,Kang Y K,Kim T Y,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[J].JAMA Oncol,2020,6(11):e204564.
[65] Gao X,Xu N,Li Z,et al.Safety and antitumour activity of cadonilimab,an anti-PD-1/CTLA-4 bispecific antibody,for patients with advanced solid tumours (COMPASSION-03):a multicentre,open-label,phase 1b/2 trial[J].Lancet Oncol,2023,24(10):1134-46.
[66] Zhu H D,Li H L,Huang M S,et al.Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001)[J].Signal Transduct Target Ther,2023,8(1):58.
[67] Xu J,Shen J,Gu S,et al.Camrelizumab in combination with apatinib in patients with advanced hepatocellular carcinoma (RESCUE):a nonrandomized,open-label,phase II trial[J].Clin Cancer Res,2021,27(4):1003-11.
[68] Qin S,Chan S L,Gu S,et al.Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310):a randomised,open-label,international phase 3 study[J].Lancet,2023,402(10408):1133-46.
[69] Kelley R K,Rimassa L,Cheng A L,et al.Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312):a multicentre,open-label,randomised,phase 3 trial[J].Lancet Oncol,2022,23(8):995-1008.
[70] Cheng A L,Qin S,Ikeda M,et al.Updated efficacy and safety data from IMbrave150:Atezolizumab plus bevacizumab vs.sorafenib for unresectable hepatocellular carcinoma[J].J Hepatol,2022,76(4):862-73.
[71] Ren Z,Xu J,Bai Y,et al.Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32):a randomised,open-label,phase 2-3 study[J].Lancet Oncol,2021,22(7):977-90.
基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2024.08.001
中图分类号:R735.7
引用信息:
[1]孙倍成.肝癌免疫治疗的挑战与机遇[J].安徽医科大学学报,2024,59(08):1295-1301.DOI:10.19405/j.cnki.issn1000-1492.2024.08.001.
基金信息:
安徽省临床医学研究转化专项(编号：2022042951070 20008);; 安徽省高校科研项目(编号：2022AH010070)
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