Targeting immune checkpoints on tumor-associated macrophages in tumor immunotherapy

Shumin Xu; Chenyang Wang; Lingge Yang; Jiaji Wu; Mengshu Li; Peng Xiao; Zhiyong Xu; Yun Xu; Kai Wang

doi:10.3389/fimmu.2023.1199631

Targeting immune checkpoints on tumor-associated macrophages in tumor immunotherapy

Front Immunol. 2023 May 29:14:1199631. doi: 10.3389/fimmu.2023.1199631. eCollection 2023.

Authors

Shumin Xu¹, Chenyang Wang¹, Lingge Yang¹, Jiaji Wu¹, Mengshu Li¹, Peng Xiao², Zhiyong Xu¹, Yun Xu¹, Kai Wang¹

Affiliations

¹ Department of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China.
² School of Medicine, Zhejiang University, Hangzhou, China.

Abstract

Unprecedented breakthroughs have been made in cancer immunotherapy in recent years. Particularly immune checkpoint inhibitors have fostered hope for patients with cancer. However, immunotherapy still exhibits certain limitations, such as a low response rate, limited efficacy in certain populations, and adverse events in certain tumors. Therefore, exploring strategies that can improve clinical response rates in patients is crucial. Tumor-associated macrophages (TAMs) are the predominant immune cells that infiltrate the tumor microenvironment and express a variety of immune checkpoints that impact immune functions. Mounting evidence indicates that immune checkpoints in TAMs are closely associated with the prognosis of patients with tumors receiving immunotherapy. This review centers on the regulatory mechanisms governing immune checkpoint expression in macrophages and strategies aimed at improving immune checkpoint therapies. Our review provides insights into potential therapeutic targets to improve the efficacy of immune checkpoint blockade and key clues to developing novel tumor immunotherapies.

Keywords: CD39; CD73; PD-1; PD-L1; SIRP-α; immune checkpoints; tumor associated macrophages.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Humans
Immune Checkpoint Inhibitors / therapeutic use
Immunotherapy*
Macrophages
Tumor Microenvironment
Tumor-Associated Macrophages*

Substances

Immune Checkpoint Inhibitors

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (No. 82100029), Zhejiang Provincial Natural Science Foundation of China (LQ22H010002), Medical Scientific Research Foundation of Zhejiang Province, China (No. 2021RC087), and Science and Technology program of Yiwu Science and Technology Bureau (No. 20-3-214).