Activation of phagocytosis by immune checkpoint blockade

Abstract

Inhibition of macrophage-mediated phagocytosis has emerged as an essential mechanism for tumor immune evasion. One mechanism inhibiting the innate response is the presence of the macrophage inhibitory molecule, signal regulatory protein-α (SIRPα), on tumor-associated macrophages (TAMs) and its cognate ligand cluster of differentiation 47 (CD47) on tumor cells in the tumor microenvironment. On the basis of a recently discovered programmed death protein 1 (PD-1) in TAMs, we discuss the potential inhibitory receptors that possess new functions beyond T cell exhaustion in this review. As more and more immune receptors are found to be expressed on TAMs, the corresponding therapies may also stimulate macrophages for phagocytosis and thereby provide extra anti-tumor benefits in cancer therapy. Therefore, identification of biomarkers and combinatorial therapeutic strategies, have the potential to improve the efficacy and safety profiles of current immunotherapies.

Keywords

CD47 / PD-1 / PD-L1 / immunotherapy / TAM / phagocytosis / macrophage

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Acknowledgements

We thank Dr. Jung-Mao Hsu for assisting with model illustration. This work was funded in part by the following: National Institutes of Health (No. CCSG CA016672); Cancer Prevention & Research Institutes of Texas (Nos. DP150052 and RP160710); National Breast Cancer Foundation, Inc.; Breast Cancer Research Foundation (No. BCRF-17-069); Patel Memorial Breast Cancer Endowment Fund; Ministry of Health and Welfare, China Medical University Hospital Cancer Research Center of Excellence (Nos. MOHW107-TDU-B-212-114024 and MOHW107-TDU-B-212-112015); and Center for Biological Pathways. In memoriam, Mrs. Serena Lin-Guo, for her courageous fight against cancer.

Compliance with ethics guidelines

Chia-Wei Li, Yun-Ju Lai, Jennifer L. Hsu, and Mien-Chie Hung declare no conflict of interest. This article does not contain any studies with human or animal subjects. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

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