Predictive biomarkers and mechanisms underlying resistance to PD1/PD-L1 blockade cancer immunotherapy
Daixi Ren, Yuze Hua, Boyao Yu, Xin Ye, Ziheng He, Chunwei Li, Jie Wang, Yongzhen Mo, Xiaoxu Wei, Yunhua Chen, Yujuan Zhou, Qianjin Liao, Hui Wang, Bo Xiang, Ming Zhou, Xiaoling Li, Guiyuan Li, Yong Li, Zhaoyang Zeng, Wei Xiong
Abstract
Immune checkpoint blockade targeting PD-1/PD-L1 has promising therapeutic efficacy in a variety of tumors, but resistance during treatment is a major issue. In this review, we describe the utility of PD-L1 expression levels, mutation burden, immune cell infiltration, and immune cell function for predicting the efficacy of PD-1/PD-L1 blockade therapy. Furthermore, we explore the mechanisms underlying immunotherapy resistance caused by PD-L1 expression on tumor cells, T cell dysfunction, and T cell exhaustion. Based on these mechanisms, we propose combination therapeutic strategies. We emphasize the importance of patient-specific treatment plans to reduce the economic burden and prolong the life of patients. The predictive indicators, resistance mechanisms, and combination therapies described in this review provide a basis for improved precision medicine.