Department of Pharmacy, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, China; College of Pharmacy, Jinan University, Guangzhou, China.
College of Pharmacy, Macau University of Science and Technology (MUST), China.
Biomed Pharmacother. 2024 Feb;171:116203. doi: 10.1016/j.biopha.2024.116203. Epub 2024 Jan 26.
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.
肿瘤免疫疗法是一种创新的抗癌疗法，在多种肿瘤类型中都显示出了令人鼓舞的疗效。其中，PD-1/PD-L1 信号通路是一种众所周知的免疫检查点，在肿瘤的免疫逃逸调节中具有重要意义。然而，相当数量的患者对抗 PD-1/PD-L1 免疫疗法产生了耐药性，从长远来看，这种疗法是无效的。本研究旨在探讨 PD-1/PD-L1 介导的肿瘤免疫治疗耐药的相关因素。首先，PD-1/PD-L1 通路的作用是促进肿瘤的免疫逃逸，强调其在自身免疫稳态中的作用。其次，分析了 PD-1/PD-L1 为基础的免疫治疗耐药的主要机制，包括肿瘤抗原缺失、T 细胞功能障碍、抑制性免疫细胞增加，以及肿瘤细胞内 PD-L1 表达的改变。还描述了改变的代谢、微生物组和 DNA 甲基化对耐药性的可能影响。最后，讨论了应对抗 PD-1/PD-L1 免疫治疗耐药性的可能解决策略，特别强调了个性化治疗方法和探索更有效的免疫治疗方案。
