免疫检查点抑制剂治疗原发性肝癌的研究进展
|
摘要
原发性肝癌(PLC)主要病理类型为肝细胞性肝癌(HCC)。肝癌的生物免疫治疗因表现出了良好的临床效果和应用前景,随着对肿瘤免疫逃逸机制的深入研究,发现免疫检查点在肿瘤免疫逃逸机制中发挥了重要作用。免疫检查点抑制剂能够阻止肿瘤的免疫逃逸,使T细胞能够持续对肿瘤细胞进行免疫监视和杀伤,起到抗肿瘤的作用。目前研究主要集中在程序性细胞死亡蛋白(PD-1)及其配体(PD-L1)、细胞毒性T淋巴细胞相关抗原-4(CTLA-4)等。就免疫检查点抑制剂治疗肝癌相关研究进展做一阐述。
引文
[1] Sznol M, Chen L. Antagonist antibodies to PD-1 and B7-H1(PD-L1)in the treatment of advanced human cancer[J]. Clin Cancer Res, 2013,19:1021-1034.
[2] Thomas NE,Busam KJ,From L,et al. Tumor-infiltrating lymphocyte grade in primary melanomas is independently associated with melanoma-specific survival in the population-basedgenes, environment and melanoma study[J]. J Clin Oncol,2013,31(33):4252.
[3] Chen DS, Mellman I. Oncology meets immunology:the cancer-immunity cycle[J]. Immunity, 2013, 39:1-10.
[4] Mahoney KM, Freeman GJ, McDermott DF. The next immunecheckpoint inhibitors:PD-1/PD-L1 blockade in melanoma[J].ClinTher, 2015, 37:764-782.
[5] Sasikumar PG, Ramachandra M. Small-Molecule Immune Checkpoint Inhibitors Targeting PD-1/PD-L1 and Other Emerging Checkpoint Pathways[J]. Biodrugs, 2018, 32(5):481-497.
[6] Tanaka A, Sakaguchi S. Regulatory T cells in cancer immunotherapy[J]. Cell Res, 2017, 27:109-118.
[7] Juneja VR, McGuire KA, Manguso RT, et al. PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity[J]. J Exp Med, 2017, 214(4):895-904.
[8] El-Khoueiry AB, 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):2492-2502.
[9] El-Khoueiry AB, Melero I, Crocenzi TS, et al. Phase I/II safety and antitumor activity of nivolumab in patients with advanced hepatocellular carcinoma(HCC):CA209-040[J]. J ClinOncol 2015, 33(suppl; abstr LBA101).
[10] Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation[J]. N Engl J Med, 2015, 372(4):320-330.
[11] Shi YW, Lin P, Ho EY, et al. Nivolumab-associated nausea and vomiting as an immune adverse event[J]. Eur J Cancer, 2017, 84:367-369.
[12] Topalian SL, Sznol M, McDermott DF, et al. Survival, durable tumor remission,and long-term safety in patients with advanced melanoma receiving nivolumab[J]. J Clin Oncol, 2014, 32(10):1020-1030.
[13] Weber JS, Postow M, Lao CD, et al. Management of Adverse Events Following Treatment With Anti-Programmed Death-1 Agents[J]. Oncologist, 2016, 21(10):1230-1240.
[14] Zimmer L, Goldinger SM, Hofmann L, et al. Neurological respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1therapy[J]. Eur J Cancer, 2016, 60:210-225.
[15] De Velasco G, Bermas B, Choueiri TK. Autoimmune Arthropathy and Uveitis as Complications of Programmed Death 1 Inhibitor Treatment[J]. Arthritis Rheumatol, 2016, 68(2):556-557.
[16] Vogel IT. CD28/CTLA-4/B7 and CD40/CD40L costimulation and activation of regulatory T cells[J]. World J Immunol, 2014, 4(2):63.
[17] Sangro B, Gomez-Martin C, de la Mata M, et al. A clinical trial of CTLA-4 blockade with tremelimumab in patients withhepatocellular carcinoma and chronic hepatitis C[J]. J Hepatol, 2013, 59(1):81-88.
[18] Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma[J]. N Engl J Med, 2015, 373:23-34.
[19] Kelley RK, Abou-Alfa GK, Bendell JC, et al. Phase I/IIstudy of durvalumab and tremelimumab inpatients with unresectable hepatocellularcarcinoma(HCC):phase I safety and efficacyanalyses[J].J Clin Oncolol, 2017, 35.
[20] Liu D, Li G, Avella DM, et al. Sunitinib represses regulatory T cells to overcome immunotolerance in a murine model of hepatocellular cancer[J]. Oncoimmunology, 2017, 7(1):e1372079.
[21] Kudo M. Immune checkpoint blockade in hepatocellular carcinoma[J]. Liver Cancer, 2015, 4:201-207.
[22] Makker V, Rasco DW, Dutcus CE. A phaseⅠb/Ⅱtrial of lenvatinib(LEN)plus pembroli-zumab(Pembro)in patients(Pts)with en-dometrial carcinoma[J]. J Clin Oncol, 2017, 35.
[23] Arizumi T, Ueshima K, Minami T, et al. Effectiveness of sorafenib in patients with transcatheter arterial chemoembolization(TACE)refractoryand intermediate-stage hepatocellular carci-noma[J]. Liver Cancer, 2015, 4:253-262.
[24] Okita K, Izumi N, Matsui O, et al. Peretinoin after curative therapy of hepatitis C-related hepatocellular carcinoma:a randomized doubleblind placebo-controlled study[J]. J Gastroenterol, 2015, 50:191-202.
[25] Pinter M, Peck-Radosavljevic M. Review article:systemic treatment of hepatocellular carcinoma[J]. Aliment Pharmacol Ther, 2018,48(6):598-609.
[26] Han X, Gu YK, Li SL, et al. Pre-treatment serum levels of soluble programmed cell death-ligand 1 predict prognosis in patients with hepatitis B-related hepatocellular carcinoma[J]. J Cancer Res Clin Oncol, 2018, 28.
[2] Thomas NE,Busam KJ,From L,et al. Tumor-infiltrating lymphocyte grade in primary melanomas is independently associated with melanoma-specific survival in the population-basedgenes, environment and melanoma study[J]. J Clin Oncol,2013,31(33):4252.
[3] Chen DS, Mellman I. Oncology meets immunology:the cancer-immunity cycle[J]. Immunity, 2013, 39:1-10.
[4] Mahoney KM, Freeman GJ, McDermott DF. The next immunecheckpoint inhibitors:PD-1/PD-L1 blockade in melanoma[J].ClinTher, 2015, 37:764-782.
[5] Sasikumar PG, Ramachandra M. Small-Molecule Immune Checkpoint Inhibitors Targeting PD-1/PD-L1 and Other Emerging Checkpoint Pathways[J]. Biodrugs, 2018, 32(5):481-497.
[6] Tanaka A, Sakaguchi S. Regulatory T cells in cancer immunotherapy[J]. Cell Res, 2017, 27:109-118.
[7] Juneja VR, McGuire KA, Manguso RT, et al. PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity[J]. J Exp Med, 2017, 214(4):895-904.
[8] El-Khoueiry AB, 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):2492-2502.
[9] El-Khoueiry AB, Melero I, Crocenzi TS, et al. Phase I/II safety and antitumor activity of nivolumab in patients with advanced hepatocellular carcinoma(HCC):CA209-040[J]. J ClinOncol 2015, 33(suppl; abstr LBA101).
[10] Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation[J]. N Engl J Med, 2015, 372(4):320-330.
[11] Shi YW, Lin P, Ho EY, et al. Nivolumab-associated nausea and vomiting as an immune adverse event[J]. Eur J Cancer, 2017, 84:367-369.
[12] Topalian SL, Sznol M, McDermott DF, et al. Survival, durable tumor remission,and long-term safety in patients with advanced melanoma receiving nivolumab[J]. J Clin Oncol, 2014, 32(10):1020-1030.
[13] Weber JS, Postow M, Lao CD, et al. Management of Adverse Events Following Treatment With Anti-Programmed Death-1 Agents[J]. Oncologist, 2016, 21(10):1230-1240.
[14] Zimmer L, Goldinger SM, Hofmann L, et al. Neurological respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1therapy[J]. Eur J Cancer, 2016, 60:210-225.
[15] De Velasco G, Bermas B, Choueiri TK. Autoimmune Arthropathy and Uveitis as Complications of Programmed Death 1 Inhibitor Treatment[J]. Arthritis Rheumatol, 2016, 68(2):556-557.
[16] Vogel IT. CD28/CTLA-4/B7 and CD40/CD40L costimulation and activation of regulatory T cells[J]. World J Immunol, 2014, 4(2):63.
[17] Sangro B, Gomez-Martin C, de la Mata M, et al. A clinical trial of CTLA-4 blockade with tremelimumab in patients withhepatocellular carcinoma and chronic hepatitis C[J]. J Hepatol, 2013, 59(1):81-88.
[18] Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma[J]. N Engl J Med, 2015, 373:23-34.
[19] Kelley RK, Abou-Alfa GK, Bendell JC, et al. Phase I/IIstudy of durvalumab and tremelimumab inpatients with unresectable hepatocellularcarcinoma(HCC):phase I safety and efficacyanalyses[J].J Clin Oncolol, 2017, 35.
[20] Liu D, Li G, Avella DM, et al. Sunitinib represses regulatory T cells to overcome immunotolerance in a murine model of hepatocellular cancer[J]. Oncoimmunology, 2017, 7(1):e1372079.
[21] Kudo M. Immune checkpoint blockade in hepatocellular carcinoma[J]. Liver Cancer, 2015, 4:201-207.
[22] Makker V, Rasco DW, Dutcus CE. A phaseⅠb/Ⅱtrial of lenvatinib(LEN)plus pembroli-zumab(Pembro)in patients(Pts)with en-dometrial carcinoma[J]. J Clin Oncol, 2017, 35.
[23] Arizumi T, Ueshima K, Minami T, et al. Effectiveness of sorafenib in patients with transcatheter arterial chemoembolization(TACE)refractoryand intermediate-stage hepatocellular carci-noma[J]. Liver Cancer, 2015, 4:253-262.
[24] Okita K, Izumi N, Matsui O, et al. Peretinoin after curative therapy of hepatitis C-related hepatocellular carcinoma:a randomized doubleblind placebo-controlled study[J]. J Gastroenterol, 2015, 50:191-202.
[25] Pinter M, Peck-Radosavljevic M. Review article:systemic treatment of hepatocellular carcinoma[J]. Aliment Pharmacol Ther, 2018,48(6):598-609.
[26] Han X, Gu YK, Li SL, et al. Pre-treatment serum levels of soluble programmed cell death-ligand 1 predict prognosis in patients with hepatitis B-related hepatocellular carcinoma[J]. J Cancer Res Clin Oncol, 2018, 28.