作者：田玉婷1，张奇1，潘新平2，李淑萍3，刘小军3

单位：1.甘肃中医药大学第一临床医学院，甘肃 兰州 730000；2.定西市人民医院 肿瘤内科，甘肃 定西 743000；3.甘肃省人民医院 放疗二科，甘肃 兰州 730099

Authors: Tian Yuting1, Zhang Qi1, Pan Xinping2, Li Shuping3, Liu Xiaojun3

Unit:  1. First School of Clinical Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, Gansu, China；2.Department of Oncology, Dingxi People's Hospital, Dingxi 743000, Gansu，China； 3.Second Department of Radiotherapy, Gansu Provincial People's Hospital, Lanzhou 730099, Gansu, China

摘要：

免疫治疗能够明显提高错配修复缺失/微卫星不稳定型结直肠癌的治疗疗效，但错配修复完整/微卫星稳定型结直肠癌对其并不敏感。肿瘤突变负荷低下可能是错配修复完整/微卫星稳定型结直肠癌免疫耐受的原因之一。信号通路的异常激活、促血管生成因子以及转化生长因子分泌的增加可能介导了错配修复完整/微卫星稳定型结直肠癌免疫治疗的原发耐药。放疗可以促进肿瘤抗原的形成和释放，并通过多种途径调节免疫反应，重塑肿瘤微环境，其与免疫治疗的联合应用为错配修复完整/微卫星稳定型结直肠癌的治疗提供了新思路。许多放疗联合免疫新辅助治疗错配修复完整/微卫星稳定型结直肠癌的临床试验正在进行当中。本文将对错配修复完整/微卫星稳定型结直肠癌免疫耐受的机制、放疗对免疫微环境的影响以及放疗联合免疫治疗在临床上的研究进展进行综述。

关键词： 微卫星稳定型；结直肠癌；免疫治疗；放疗；错配修复蛋白

Abstract：

Immunotherapy can significantly improve the treatment efficacy of colorectal cancer of deficient mismatch repair/ microsatellite instability, but proficient mismatch repair/microsatellite stable colorectal cancer patients are not sensitive to it. Low tumor mutation burden may be one of the reasons for immune tolerance in colorectal cancer of proficient mismatch repair/microsatellite stability. Abnormal activation of signaling pathways, increased secretion of pro-angiogenic factors and transforming growth factors may mediate primary drug resistance of immunotherapy of proficient mismatch repair/microsatellite stable colorectal cancer. Increasing the sensitivity of immunotherapy in proficient mismatch repair/microsatellite stable colorectal cancer is an important challenge in the treatment of colorectal cancer. Comprehensive treatment including immunotherapy is a very effective strategy for the treatment of malignant tumors. Radiotherapy can promote the formation and release of tumor antigens, regulate the immune response through a variety of ways, and reshape the tumor microenvironment. Radiotherapy combined with immunotherapy provides a new idea for the treatment of proficient mismatch repair/microsatellite stable colorectal cancer. Many clinical trials of neoadjuvant radiotherapy combined with immunotherapy for proficient mismatch repair/microsatellite stable colorectal cancer are ongoing. In this review, the mechanism of immune tolerance of proficient mismatch repair/microsatellite stable colorectal cancer, the effect of radiotherapy on the immune microenvironment, and the clinical research progress of radiotherapy combined with immunotherapy in proficient mismatch repair/microsatellite stable colorectal cancer were summarized.

Key Words:  Microsatellite stability; Colorectal cancer; Immunotherapy; Radiotherapy; Mismatch repair protein

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