The role of PD-1/PD-L1 axis and macrophage in the progression and treatment of cancer

  • Jiajing Cai
  • Qi Qi
  • Xuemeng Qian
  • Jia Han
  • Xinfang Zhu
  • Qi ZhangEmail author
  • Rong XiaEmail author
Review – Cancer Research



During the past decades, PD-1/PD-L1 axis blockade has become a remarkable promising therapy which has exerted durable anti-tumor effect and long-term remissions on part of cancers. However, there are still some patients which do not show good response to the PD-1/PD-L1 targeted monotherapy. Till now, the widely accepted anti-tumor mechanism of PD-1/PD-L1 blockade is rejuvenating T cells, there is lack of studies which focus on other components of the tumor environment in the treatment of cancer with PD-1/PD-L1 blockade, especially the complicated relationship between macrophages and PD-1/PD-L1 pathway during the progression and treatment of cancer.


The relevant literatures from PubMed have been reviewed in this article.


Even though the widely accepted anti-tumor mechanism of PD-1/PD-L1 blockade therapy is rejuvenating T cells, latest studies have demonstrated the complicated relationship between macrophages and PD-1/PD-L1 pathway during the progression and treatment of cancer and their engagement has serious implications for the therapeutic effect of PD-1/PD-L1 blockade agents. We focus on the dual regulation mechanisms between PD-1/PD-L1 axis and macrophages, and further clarify the mechanisms of resistance to PD-1/PD-L1 inhibitors related with macrophages.


The combination of PD-1/PD-L1 blockade and macrophage-targeted therapy will exert synergetic anti-tumor effect and shape the future of cancer immunology and immunotherapy.


PD-1 PD-L1 Macrophage T cell Combination therapy 



This study is supported by National Natural Science Foundation of China (81670173 and 81570166) and Public Health Leading Academic Discipline Project supported by Shanghai Municipal Commission of Health and Family Planning (No. 15GWZK0501).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Transfusion MedicineHuashan Hospital, Fudan UniversityShanghaiPeople’s Republic of China

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