Predictive biomarkers and mechanisms underlying resistance to PD1/PD-L1 blockade cancer immunotherapy

Daixi Ren(Central South University), Yuze Hua(Central South University), Boyao Yu(Central South University), Xin Ye(Central South University), Ziheng He(Central South University), Chunwei Li(Central South University), Jie Wang(Central South University), Yongzhen Mo(Central South University), Xiaoxu Wei(Central South University), Yunhua Chen(Central South University), Yujuan Zhou(Central South University), Qianjin Liao(Central South University), Hui Wang(Central South University), Bo Xiang(Central South University), Ming Zhou(Central South University), Xiaoling Li(Central South University), Guiyuan Li(Central South University), Yong Li(Baylor College of Medicine), Zhaoyang Zeng(Central South University), Wei Xiong(Central South University)
Molecular Cancer
January 30, 2020
10.1186/s12943-020-1144-6
Cited by 329Open Access
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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.

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