2018, Volume 12, Issue 4
Frontiers of Medicine >> 2018, Volume 12, Issue 4 doi: 10.1007/s11684-018-0657-5
Activation of phagocytosis by immune checkpoint blockade
1. Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. 2.Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
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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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