Sun Liting, Meng Cong, Zhang Xiao, Gao Jiale, Wei Pengyu, Zhang Jie, Zhang Zhongtao
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University and National Clinical Research Center for Digestive Diseases, Beijing, China.
Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Front Pharmacol. 2023 Apr 28;14:1167670. doi: 10.3389/fphar.2023.1167670. eCollection 2023.
Programmed cell death protein (PD-1) is an important immunosuppressive molecule, which can inhibit interaction between PD-1 and its ligand PD-L1, further enhancing the T cell response and anti-tumor activity, which is called immune checkpoint blockade. Immunotherapy, represented by immune checkpoint inhibitors, has opened up a new era of tumor treatment and is gradually being applied to colorectal cancer recently. Immunotherapy was reported could achieve a high objective response rate (ORR) for colorectal cancer with high microsatellite instability (MSI), thus opening up a new era of colorectal cancer immunotherapy. Along with the increasing use of PD1 drugs in colorectal cancer, we should pay more attention to the adverse effects of these immune drugs while seeing the hope. Immune-related adverse events (irAEs) caused by immune activation and immune homeostasis during anti-PD-1/PD-L1 therapy can affect multi-organ and even be fatal in serious cases. Therefore, understanding irAEs is essential for their early detection and appropriate management. In this article, we review the irAEs that occur during the treatment of colorectal cancer patients with PD-1/PD-L1 drugs, analyze the current controversies and challenges, and point out future directions that should be explored, including exploring efficacy predictive markers and optimizing the paradigm of individualized immunotherapy.
程序性细胞死亡蛋白(PD-1)是一种重要的免疫抑制分子,它能够抑制PD-1与其配体PD-L1之间的相互作用,进而增强T细胞反应和抗肿瘤活性,这被称为免疫检查点阻断。以免疫检查点抑制剂为代表的免疫疗法开启了肿瘤治疗的新时代,并且最近逐渐应用于结直肠癌治疗。据报道,免疫疗法对微卫星高度不稳定(MSI)的结直肠癌可实现较高的客观缓解率(ORR),从而开启了结直肠癌免疫治疗的新时代。随着PD1药物在结直肠癌中使用的增加,我们在看到希望的同时,也应更加关注这些免疫药物的不良反应。抗PD-1/PD-L1治疗期间由免疫激活和免疫稳态引起的免疫相关不良事件(irAEs)可累及多个器官,严重时甚至会致命。因此,了解irAEs对于其早期发现和恰当处理至关重要。在本文中,我们综述了使用PD-1/PD-L1药物治疗结直肠癌患者期间发生的irAEs,分析了当前存在的争议和挑战,并指出了应探索的未来方向,包括探索疗效预测标志物和优化个体化免疫治疗模式。