PD-L1阴性及低表达晚期胃癌免疫检查点抑制剂应用临床研究进展

Progress of immune checkpoint inhibitors in advanced gastric cancer with PD-L1negative and low expression

目的对免疫检查点抑制剂(ICIs)在晚期胃癌尤其是细胞程序性死亡-配体1(PD-L1)阴性及低表达胃癌患者中的研究进展进行综述分析,为其临床应用提供参考。方法以“胃癌、免疫治疗、免疫检查点抑制剂”为中文检索词,以“gastric cancer、immunotherapy、immune checkpoint inhibitor、PD-L1”为英文检索词,检索PubMed和中国知网数据库2000-01-01-2024-02-01发表的相关文献。纳入标准:(1)有晚期胃癌患者参与的临床研究;(2)免疫治疗和生物标志物;(3)PD-L1和ICIs疗效。排除标准:重复、数据不全的研究。最终纳入文献63篇,其中中文文献1篇,英文文献62篇。结果ICIs在晚期胃癌中得到广泛应用。总体来讲,PD-L1的表达水平越高,晚期胃癌患者的免疫治疗疗效越好。而PD-L1联合阳性评分(CPS)低表达(CPS<5)的晚期胃癌患者中,ICIs是否能够显著延长患者的生存尚不明确。一方面,应将CPS<5人群进一步细分为CPS 1~4和CPS<1人群,前者可能从免疫治疗中获益,后者则很难获益。另一方面,由于PD-L1本身表达的异质性及检测方法的局限性,其免疫疗效预测价值有限,应结合其他生物标志物或临床特征进行判断。需要开展更大规模、更深入、更精准的研究,探索和优化PD-L1低表达胃癌患者的治疗方案。结论ICIs在晚期胃癌治疗中起重要作用,PD-L1表达水平与免疫疗效密切相关,但不是唯一确定因素。ICIs在PD-L1低表达及阴性患者中的获益情况应区别看待,并需要大型临床研究进一步验证。

Objective To review the research progress of immune checkpoint inhibitors(ICIs)in advanced gastric cancer,especially in patients with programmed death-ligand 1(PD-L1)negative and low expression,and to provide reference for its clinical application.Methods Using"gastric cancer,immunotherapy,immune checkpoint inhibitor,programmed death-ligand 1(PD-L1)"as the keywords,the relevant literature were searched from PubMed,China National Knowledge Infrastructure(CNKI)Database from January 1,2000to February 1,2024.Inclusion criteria:(1)clinical studies involving patients with advanced gastric cancer;(2)immunotherapy and biomarkers;(3)efficacy of PD-L1and ICIs.Exclusion criteria:studies with duplicate and incomplete data were excluded.Finally,63articles were included.Among them,there was 1Chinese literature and 62English literature.Result ICIs is widely used in advanced gastric cancer.In general,the higher the expression level of PD-L1,the better the immunotherapy efficacy of patients with advanced gastric cancer.However,in advanced gastric cancer patients with low PD-L1combined positive score(CPS)expression(CPS<5),it is unclear whether ICIs can significantly prolong the survival of patients.On the one hand,the CPS<5population should be further subdivided into CPS 1-4and CPS<1populations,the former of which may benefit from immunotherapy,but the latter of which is difficult to benefit.On the other hand,due to the heterogeneity of PD-L1expression and the limitations of detection methods,its value in predicting immune efficacy is limited,and it should be combined with other biomarkers or clinical characteristics to judge.Larger,deeper and more precise studies are needed to explore and optimize treatment options for patients with low PD-L1expression of gastric cancer.Conclusions ICIs plays an important role in the treatment of advanced gastric cancer,and the expression level of PD-L1is closely related to the immune efficacy,but it is not the only determining factor.The benefits of ICIs in patients with low and negative PD-L1expression should be differentiated and further validated in large clinical studies.