• Jiajing Cai, Qi Qi, Xuemeng Qian, Jia Han, Xinfang Zhu, Qi Zhang, and Rong Xia.
• Department of Transfusion Medicine, Huashan Hospital, Fudan University, 12 Urumqi Middle Road, Shanghai, 200040, People's Republic of China.
• J. Cancer Res. Clin. Oncol. 2019 Jun 1; 145 (6): 1377-1385.

PurposeDuring 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.MethodsThe relevant literatures from PubMed have been reviewed in this article.ResultsEven 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.ConclusionThe 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.

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