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

作　　者：Mengjia Song Xinfeng Chen Liping Wang Yi Zhang 

机构地区：[1]Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China [2]Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China [3]School of Life Sciences, Zhengzhou University, Zhengzhou 450052, China [4]Key Laboratory for Tumor Immunology and Biotherapy of Henan Province, Zhengzhou 450052, China

出　　处：《Chinese Journal of Cancer Research》2018年第2期157-172,共16页中国癌症研究（英文版）

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

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 patients.However, 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.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 patients.However, 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.

关 键 词：Cancer immunotherapy combination therapy PD-1 PD-L 1 resistance tumor microenvironment 

分 类 号：R730.5[医药卫生—肿瘤]