Blockade of the Phagocytic Receptor MerTK on Tumor-Associated Macrophages Enhances P2X7R-Dependent STING Activation by Tumor-Derived cGAMP.
Publication Title
Immunity
Document Type
Article
Publication Date
2-18-2020
Keywords
MerTK; P2X7R; STING; cGAS; cancer immunotherapy; efferocytosis; innate immunity; tumor-associated macrophage; type I IFN
Abstract
Clearance of apoptotic cells by macrophages prevents excessive inflammation and supports immune tolerance. Here, we examined the effect of blocking apoptotic cell clearance on anti-tumor immune response. We generated an antibody that selectively inhibited efferocytosis by phagocytic receptor MerTK. Blockade of MerTK resulted in accumulation of apoptotic cells within tumors and triggered a type I interferon response. Treatment of tumor-bearing mice with anti-MerTK antibody stimulated T cell activation and synergized with anti-PD-1 or anti-PD-L1 therapy. The anti-tumor effect induced by anti-MerTK treatment was lost in Sting
Clinical Institute
Cancer
Specialty/Research Institute
Earle A. Chiles Research Institute
Specialty/Research Institute
Oncology
