结直肠癌免疫检查点抑制剂研究进展

Research progress of immune checkpoint inhibitors for colorectal cancer

近十年来,结直肠癌免疫治疗取得了长足的进展,尤其对于错配修复缺陷(dMMR)/高微卫星不稳定性(MSI-H)表型的结直肠癌,免疫治疗具有持续的治疗反应,并取得了显著的临床疗效。但是大多数转移性结直肠癌为非错配修复缺陷(pMMR)或微卫星稳定(MSS)状态,这部分患者从免疫检查点抑制剂(ICIs)中获益较少。随着ICIs在结直肠癌中临床试验的广泛开展,免疫治疗因确定的疗效,逐步扩大了适应证,对于dMMR/MSI-H的晚期结直肠癌患者,已成为标准一线治疗方案。而对于pMMR/MSS患者,ICIs通过联合化疗及靶向治疗,也显示出了潜在的治疗效果。本文主要就ICIs在结直肠癌中的应用展开讨论,分析肿瘤与免疫系统之间的相互关系,并概述结直肠癌的免疫学特征及分类以及ICIs在结直肠癌治疗中的最新进展。

In recent ten years,immunotherapy for colorectal cancer has made great progress.Especially for colorectal cancer(CRC)with deficient mismatch repair(dMMR)/microsatellite instability high(MSI-H)phenotype,immunotherapy has sustained response and achieved significant clinical efficacy.However,most of the metastatic colorectal cancer patients are in the state of mismatch repair defect(pMMR)or microsatellite stable(MSS).These patients benefit less from immune checkpoint inhibitors(ICIs).With the extensive development of ICIS in colorectal cancer clinical trials,immunotherapy has gradually expanded the indications because of its definite efficacy.For patients with advanced colorectal cancer with dMMR/MSIH,it has become the standard first-line treatment.For pMMR/MSS patients,ICIs also showed potential therapeutic effect through combined chemotherapy and targeted therapy.In this review,we mainly discuss the application of ICIs in colorectal cancer,explain the relationship between tumor and immune system,and summarize the immunological characteristics and classification of CRC,as well as the latest progress of ICIs in the treatment of CRC.