Future of anti-PD-1/PD-L1 applications： Combinations with other therapeutic regimens

作     者：Mengjia Song Xinfeng Chen Liping Wang Yi Zhang 

作者机构：Biotherapy Center the First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 China Cancer Center the First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 China School of Life Sciences Zhengzhou University Zhengzhou 450052 China Key Laboratory for Tumor Immunology and Biotherapy of Henan Province Zhengzhou 450052 China 

出 版 物：《Chinese Journal of Cancer Research》 (中国癌症研究（英文版）)

年 卷 期：2018年第30卷第2期

页      面：157-172页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by grants from the National Natural Science Foundation of China (No. 81171986) the Ministry of Public Health (No. 201501004) 

主　　题：Cancer immunotherapy combination therapy PD-1 PD-L 1 resistance tumor microenvironment 

摘      要：Programmed cell death 1（PD-1）/programmed cell death 1 ligand（PD-L1） blockade has shown promising effects in cancer immunotherapy. Removing the so-called ＂brakes＂ on T cell immune responses by blocking the PD-1/PDL1 check point should boost anti-tumor immunity and provide durable tumor regression for cancer ***, 30%–60% of patients show no response to PD-1/PD-L1 blockade. Thus, it is urgent to explore the underlying resistance mechanisms to improve sensitivity to anti-PD-1/PD-L1 therapy. We propose that the mechanisms promoting resistance mainly include T cell exclusion or exhaustion at the tumor site,immunosuppressive factors in the tumor microenvironment（TME）, and a range of tumor-intrinsic factors. This review highlights the power of studying the cellular and molecular mechanisms of resistance to improve the rational design of combination therapeutic strategies that can be translated to the clinic. Here, we briefly discuss the development of PD-1/PD-L1 blockade agents and focus on the current issues and future prospects for potential combinatorial therapeutic strategies that include anti-PD-1/PD-L1 therapy, based upon the available preclinical and clinical data.