Abushukair Hassan, Ababneh Obada, Zaitoun Sara, Saeed Anwaar
Faculty of Medicine, Jordan University of Science and Technology, 22110, Irbid, Jordan.
Faculty of Medicine, Yarmouk University, 21163, Irbid, Jordan.
Cancer Treat Res Commun. 2022;33:100643. doi: 10.1016/j.ctarc.2022.100643. Epub 2022 Sep 24.
Immune checkpoint inhibitors (ICIs) have significantly advanced colorectal cancer treatment in recent years. Antibodies that target the proteins programmed cell death-1 (PD-1), programmed cell death-1 ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are among the ICIs that are currently being used in clinical practice. However, in colorectal cancer, ICI's effectiveness is limited to a fraction of patients with microsatellite instability-high (MSI-H), which only accounts for about 5% of advanced cases. The tumor microenvironment and intrinsic changes in tumor cells are just a couple of the many mechanisms that play a role in ICI primary or secondary resistance. In order to advance precision medicine and broaden the population benefiting from ICI, this paper highlights the main underlying mechanisms of ICIs resistance and suggested techniques to overcome it.
近年来，免疫检查点抑制剂（ICIs）显著推动了结直肠癌的治疗。靶向程序性细胞死亡蛋白1（PD-1）、程序性细胞死亡蛋白1配体1（PD-L1）和细胞毒性T淋巴细胞相关蛋白4（CTLA-4）的抗体属于目前临床实践中使用的ICIs。然而，在结直肠癌中，ICI的有效性仅限于一小部分微卫星高度不稳定（MSI-H）的患者，而这部分患者仅占晚期病例的约5%。肿瘤微环境和肿瘤细胞的内在变化只是导致ICI原发性或继发性耐药的众多机制中的一部分。为了推进精准医学并扩大受益于ICI的人群，本文重点介绍了ICI耐药的主要潜在机制以及克服耐药的建议技术。
