恶性肿瘤免疫治疗的耐药机制

Resistance Mechanisms of Cancer Immunotherapy

免疫检查点抑制剂(immune checkpoint blockade,ICB)的发现及应用在恶性肿瘤治疗上取得了重大进展,现已有多种ICB应用于临床,包括抗细胞毒性T淋巴细胞相关抗原4(cytotoxic T-lymphocyte antigen 4,CTLA-4)单抗、抗程序性细胞死亡受体1(programmed cell death-1,PD-1)及其配体PD-L1(programmed cell death-ligand1)单抗等。但是并非所有患者都能获益,ICB治疗有效的患者会发生耐药,部分患者初治就对ICB不敏感。因此,揭示ICB的耐药机制及如何克服耐药显得至关重要。全文就已发现的ICB耐药机制及克服耐药的多种联合治疗模式进行综述,为临床研究及临床实践提供新思路。

The discovery and application of immune checkpoint blockade(ICB) have made unprecedented breakthroughs in the treatment of malignant tumors. At present,many ICBs have been used in clinical practice,including antibodies targets the cytotoxic T-lymphocyte antigen 4(CTLA-4),programmed cell death-1(PD-1) and programmed cell death-ligand1(PD-L1). However,not all patients can benefit from the immunotherapy. Patients who initially respond well to ICB will develop resistance and some even can't get benefit at the beginning. Therefore,it is crucial to reveal the resistance mechanisms of ICB and the solutions to overcome the drug resistance. This article reviews the current resistance mechanisms of ICB and the combination therapies to overcome the resistance in order to provide new clues for clinical research and practice.