中国实用外科杂志

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不同微卫星状态结直肠癌免疫治疗进展与挑战

梁    欢,李    健   

  1. 北京大学肿瘤医院暨北京市肿瘤防治研究所 恶性肿瘤发病机制及转化研究教育部重点实验室 消化肿瘤内科,北京 100142  
  • 出版日期:2024-07-01

  • Online:2024-07-01

摘要: 近年来,关于微卫星稳定(MSS)和微卫星高度不稳定(MSI-H)结直肠癌免疫治疗的研究不断开展。KEYNOTE-177、CheckMate-142等研究结果为MSS型和MSI-H型结直肠癌的免疫治疗提供了重要的临床数据支持。MSI-H型结直肠癌对常规化疗不敏感,往往预后较差,但由于存在高突变负荷和新抗原,对免疫检查点抑制剂[如程序性死亡受体1(PD-1)抑制剂、细胞毒性T淋巴细胞相关抗原-4(CTLA -4)抑制剂]响应良好。而MSS型结直肠癌突变负荷较低,免疫原性较弱,故对免疫治疗的响应较差。目前,通过探索组合疗法,改进免疫调节策略,如靶向肿瘤微环境中的免疫抑制细胞或因子,可以改善MSS型结直肠癌的免疫治疗效果以及寻找有效的生物标记物。此外,一些研究还探索了免疫治疗在结直肠癌新辅助治疗中的应用以及与其他治疗手段的联合应用等问题。这些研究不仅丰富了对MSS型和MSI-H型结直肠癌免疫治疗的认识,还为临床提供了更多的治疗选择。 

关键词: 结直肠癌, 微卫星稳定, 微卫星高度不稳定, 免疫治疗

Abstract: In recent years, research on immune therapy for colorectal cancer with microsatellite stability (MSS) and microsatellite instability-high (MSI-H) has been continuously emerging. Studies such as KEYNOTE-177 and CheckMate-142 provide important clinical data support for immunotherapy of MSS and MSI-H colorectal cancer. MSI-H type colorectal cancer is not sensitive to conventional chemotherapy and often has a poor prognosis. However, due to the presence of a high mutation burden and new antigens, it responds well to immune checkpoint inhibitors such as programmed death receptor 1 (PD-1) inhibitors and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitors. However, MSS-type colorectal cancer has a lower mutation burden and weaker immunogenicity, resulting in a poorer response to immunotherapy. At present, by exploring combination therapy and improving immune regulation strategies, such as targeting immunosuppressive cells or factors in the tumor microenvironment, the immunotherapeutic effect of MSS-type colorectal cancer can be improved and effective biomarkers can be found. In addition, some studies have also explored the application of immunotherapy in neoadjuvant therapy for colorectal cancer and its combination with other treatment methods. These studies not only enrich the understanding of immunotherapy for MSS and MSI-H colorectal cancer but also provide more treatment options for clinical practice.

Key words: colorectal cancer, microsatellite stable, microsatellite instability-high, immunotherapy