He Tao, Hu Chencheng, Li Shichao, Fan Yao, Xie Fei, Sun Xin, Jiang Qingfeng, Chen Weidong, Jia Yingtian, Li Wusheng
The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou City, Sichuan Province, China.
Heliyon. 2024 Jun 15;10(12):e33144. doi: 10.1016/j.heliyon.2024.e33144. eCollection 2024 Jun 30.
Immunotherapy has been an advanced and effective approach to treating various types of solid tumors in recent years, and the most successful strategy is immune checkpoint inhibitors (ICIs), which have shown beneficial effects in patients with colorectal cancer (CRC). Drug resistance to ICIs is usually associated with CD8 T-cells targeting tumor antigens; thus, CD8 T-cells play an important role in immunotherapy. Unfortunately, Under continuous antigen stimulation, tumor microenvironment(TME), hypoxia and other problems it leads to insufficient infiltration of CD8 T-cells, low efficacy and mechanism exhaustion, which have become obstacles to immunotherapy. Thus, this article describes the relationship between CRC and the immune system, focuses on the process of CD8 T-cells production, activation, transport, killing, and exhaustion, and expounds on related mechanisms leading to CD8 T-cells exhaustion. Finally, this article summarizes the latest strategies and methods in recent years, focusing on improving the infiltration, efficacy, and exhaustion of CD8 T-cells, which may help to overcome the barriers to immunotherapy.
近年来,免疫疗法已成为治疗各类实体瘤的一种先进且有效的方法,最成功的策略是免疫检查点抑制剂(ICIs),其已在结直肠癌(CRC)患者中显示出有益效果。对ICIs的耐药性通常与靶向肿瘤抗原的CD8 T细胞相关;因此,CD8 T细胞在免疫疗法中发挥着重要作用。不幸的是,在持续的抗原刺激下,肿瘤微环境(TME)、缺氧以及其导致的CD8 T细胞浸润不足、疗效低下和机制耗竭等问题,已成为免疫疗法的障碍。因此,本文描述了结直肠癌与免疫系统之间的关系,重点关注CD8 T细胞的产生、激活、运输、杀伤和耗竭过程,并阐述导致CD8 T细胞耗竭的相关机制。最后,本文总结了近年来的最新策略和方法,重点在于改善CD8 T细胞的浸润、疗效和耗竭情况,这可能有助于克服免疫疗法的障碍。