胃癌PD-1/PD-L1免疫检查点抑制剂免疫治疗影响因素分析

Influencing factors of PD-1/PD-L1 immune checkpoint inhibitor immunotherapy for gastric cancer

胃癌发病率、死亡率均高,晚期治疗手段有限。近年来,随着靶向药物(包括VEGFR-2拮抗剂、抗HER-2抗体)和免疫治疗药物(如抗CTLA-4抗体、抗PD-1/PD-L1抗体)的问世,晚期胃癌的疗效得到提升。目前研究较多的PD-1及其配体PD-L1抑制剂相关临床数据取得了阶段性成功,但究竟哪些因素影响PD-1/PD-L1免疫检查点抑制剂(checkpoint inhibitors, CPI)免疫治疗的疗效,且如何选择获益人群以及建立预后评价体系是目前亟待解决的问题。因此,本文从全身化疗、肠道菌群、微卫星不稳定(microsatellite instability, MSI)、幽门螺旋杆菌(helicobacter pylori, Hp)感染、EB病毒、肿瘤突变负荷(tumor mutation burden, TMB)、肿瘤浸润淋巴细胞等7个方面阐述影响PD-1/PD-L1抑制剂免疫治疗效果的因素,以期为临床工作提供新思路。

Gastric cancer has high morbidity and mortality, and limited treatment options for advanced cancer. In recent years, with the advent of targeted drugs(including VEGFR-2 antagonists, anti-HER-2 antibodies) and immunotherapeutics(such as anti-CTLA-4 antibodies, anti-PD-1/PD-L1 antibodies), the efficacy of advanced gastric cancer has been increased. Currently, the clinical data of PD-1 and its ligand PD-L1 inhibitors have achieved phased success, but which factors affect the efficacy of PD-1/PD-L1 immune checkpoint inhibitors immunotherapy, and how to select the benefited patient population and establish the prognosis evaluation system are the urgent problems to be solved. Therefore, this review elaborated the factors affecting the immunotherapy effects of PD-1/PD-L1 inhibitors from the aspects of systemic chemotherapy, intestinal microbiota, MSI, Hp infection, Epstein-Barr virus, TMB, and tumor infiltrating lymphocytes, in order to provide new ideas for clinical work.