Blockade of the Phagocytic Receptor MerTK on Tumor-Associated Macrophages Enhances P2X7R-Dependent STING Activation by Tumor-Derived cGAMP.
MerTK; P2X7R; STING; cGAS; cancer immunotherapy; efferocytosis; innate immunity; tumor-associated macrophage; type I IFN
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
Earle A. Chiles Research Institute
Zhou, Yi; Fei, Mingjian; Zhang, Gu; Liang, Wei-Ching; Lin, WeiYu; Wu, Yan; Piskol, Robert; Ridgway, John; McNamara, Erin; Huang, Haochu; Zhang, Juan; Oh, Jaehak; Patel, Jaina M; Jakubiak, Diana; Lau, Jeff; Blackwood, Beth; Bravo, Daniel D; Shi, Yongchang; Wang, Jianyong; Hu, Hong-Ming; Lee, Wyne P; Jesudason, Rajiv; Sangaraju, Dewakar; Modrusan, Zora; Anderson, Keith R; Warming, Søren; Roose-Girma, Merone; and Yan, Minhong, "Blockade of the Phagocytic Receptor MerTK on Tumor-Associated Macrophages Enhances P2X7R-Dependent STING Activation by Tumor-Derived cGAMP." (2020). Articles, Abstracts, and Reports. 2866.