Tumor immunotherapy resistance: Revealing the mechanism of PD-1 / PD-L1-mediated tumor immune escape

• Published in: Biomedicine & pharmacotherapy 2024-02, Vol.171, p.116203-116203, Article 116203
• Main Authors: Cui, Jia-Wen, Li, Yao, Yang, Yang, Yang, Hai-Kui, Dong, Jia-Mei, Xiao, Zhi-Hua, He, Xin, Guo, Jia-Hao, Wang, Rui-Qi, Dai, Bo, Zhou, Zhi-Ling
• Format: Article
• Language: English
• Subjects: Anti-PD-1/PD-L1 therapy; Immune escape; Immunotherapy resistance; PD-1/PD-L1; Tumor immunotherapy
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2024.116203

Tumor immunotherapy, an innovative anti-cancer therapy, has showcased encouraging outcomes across diverse tumor types. Among these, the PD-1/PD-L1 signaling pathway is a well-known immunological checkpoint, which is significant in the regulation of immune evasion by tumors. Nevertheless, a considerable number of patients develop resistance to anti-PD-1/PD-L1 immunotherapy, rendering it ineffective in the long run. This research focuses on exploring the factors of PD-1/PD-L1-mediated resistance in tumor immunotherapy. Initially, the PD-1/PD-L1 pathway is characterized by its role in facilitating tumor immune evasion, emphasizing its role in autoimmune homeostasis. Next, the primary mechanisms of resistance to PD-1/PD-L1-based immunotherapy are analyzed, including tumor antigen deletion, T cell dysfunction, increased immunosuppressive cells, and alterations in the expression of PD-L1 within tumor cells. The possible ramifications of altered metabolism, microbiota, and DNA methylation on resistance is also described. Finally, possible resolution strategies for dealing with anti-PD-1/PD-L1 immunotherapy resistance are discussed, placing particular emphasis on personalized therapeutic approaches and the exploration of more potent immunotherapy regimens. [Display omitted] •Tumor immune escape mechanisms contribute to immunotherapy resistance.•PD-1/PD-L1 signaling pathway regulates immune evasion by tumors.•Tumor antigen deletion and T cell impact response to anti-PD-1/PD-L1 therapy.•Alterations in PD-L1 expression and metabolism impact immunotherapy resistance.•Targeted therapies and personalized treatment promise to overcome drug resistance.