免疫检查点抑制剂联合治疗在微卫星稳定型结直肠癌治疗中的研究进展  

rogress of ICIs combination therapy in MSS colorectal cancer

作　　者：宁臣功 孙岩波[1] 孙锋[1] Ning Chengong;Sun Yanbo;Sun Feng(Department of Gastrointestinal Surgery,The Second Affiliated Hospital of Kunming Medical University,Kunming 650032,Yunnan,China)

机构地区：[1]昆明医科大学第二附属医院胃肠外科,云南昆明650032

出　　处：《肿瘤代谢与营养电子杂志》2023年第2期277-282,共6页Electronic Journal of Metabolism and Nutrition of Cancer

基　　金：国家自然科学基金(81960508);云南省科技厅科技计划项目(202001AY070001-053);云南省科技厅科技计划项目(2019FE001);云南省医学学科后备人才培养计划(H-2018067)。

摘　　要：结直肠癌是消化系统最常见的恶性肿瘤,发病率在肿瘤中排第3位,死亡率排第2位,对患者的生存期和生活质量造成了严重威胁。免疫检查点抑制剂(ICIs)已成为错配修复缺陷或微卫星高度不稳定(MSI-H/d MMR)结直肠癌的一线及后线治疗方案的重要组成,然而,MSI-H/d MMR结直肠癌仅占所有转移性结直肠癌的4%~5%,且对于微卫星稳定型(MSS)结直肠癌患者,由于肿瘤的异质性和复杂的免疫异质性肿瘤微环境,ICIs单药往往无法克服这些因子而出现应答率不高或出现继发性耐药,因此仅使用单一ICIs基本无效。目前多采用联合治疗策略如抗程序性死亡蛋白受体-1(PD-1)和细胞毒性T淋巴细胞相关蛋白4(CTLA-4)的联合治疗,ICIs联合放疗,ICIs联合细胞外信号调节激酶(MEK)抑制剂和血管内皮生长因子(VEGF)抑制剂,以及ICIs联合溶瘤病毒等提高MSS/错配修复功能完整(pMMR)结直肠癌患者对治疗的应答率。虽然上述联合治疗策略取得不错的近期疗效,在治疗转移性结直肠癌(mCRC)患者中很有前景,但多为单臂小样本探索性研究,数据指向并不完全稳定一致,安全性和有效性还需更多大样本的前瞻性临床试验验证,同时也需Ⅲ期临床研究的确认和证实。本文旨在对MSS结直肠癌ICIs联合治疗研究进展进行综述。Colorectal cancer is the most common malignant tumor of digestive system,ranking the third in incidence and the second in mortality,which poses a serious threat to the survival and quality of life of patients.Immune checkpoint inhibitors have become an important component of the first-line and late-line treatment regimens for MSI-H/dMMR colorectal cancer.However,MSI-H/dMMR colorectal cancer accounts for only 4%~5% of all metastatic colorectal cancers,and for MSS/pMMR colorectal cancer patients,due to tumor heterogeneity and complex immunologically heterogeneous tumor microenvironment,immune checkpoint inhibitors alone often cannot overcome these factors and have low response rate or secondary drug resistance,so the use of single ICIs is basically inefective.At present,combination therapy strategies such as anti-PD-1 and CTLA-4,ICIs combined with radiotherapy,ICIs combined with MEK inhibitor and VEGF inhibitor,ICIs combined with oncolytic virus,double immunotherapy combined with targeted therapy are adopted to improve the response rate of MSS/pMMR colorectal cancer patients.Although the above-mentioned combination therapy strategy has achieved good short-term efficacy and has great prospects in the treatment of mCRC patients,most of them are single-arm small-sample exploratory studies,and the data are not completely stable and consistent.The safety and effectiveness need to be verified by more large-sample prospective clinical trials,and also need to be confirmed and confirmed by phase II clinical studies.This article aims to review the progress of ICIs combination therapy for MSS colorectal cancer.

关 键 词：微卫星稳定型 结直肠癌 免疫治疗 联合治疗 

分 类 号：R735.34[医药卫生—肿瘤]