Abstract A084: Regulation of Anti-Tumor Immune Response by EphA2 Receptor Tyrosine Kinase

Abstract Eph receptors are the largest subfamily of receptor tyrosine kinases (RTK). Overexpression of EphA2 is a common signature for many types of human solid cancer including glioblastoma, melanoma and cancers of breast, lung, colon, pancreas and prostate, which is correlated with poor prognosis, through incompletely understood mechanisms. We report here that EphA2 knock-out potently suppressed tumor development in several multiple syngeneic mouse cancer models. Such effects were missing in immune deficient mice, suggesting the involvement of immune components. Immunophenotyping of the tumors showed elevated T cell infiltration and activity accompanied by reduced MDSC population in the EphA2 KO tumors. Single cell transcriptomic analysis and cytokine measurements supported these results showing increased production of CCL5, CXCL9, CXCL10 and IFNg in the EphA2 KO tumors. Analysis on tumors at very early time points revealed higher levels of CXCL1 and CXCL2 which recruits suppressive MDSCs. In support, larger population of MDSCs was found in PBMCs from the control tumor-bearing mice than those bearing EphA2 KO tumors. These results suggest that EphA2 in cancer cells drives the production of CXCL1 and CXCL2 to recruit suppressive MDSCs to the tumor site, thus subvert the host anti-tumor immune surveillance. Targeting the overexpressed EphA2 in cancer can help reshape the tumor immune microenvironment towards type I anti-tumor immune response. Citation Format: Xioajun Roger Shi, Ryan Lingerak, Soyeon Kim, Bingcheng Wang. Regulation of Anti-Tumor Immune Response by EphA2 Receptor Tyrosine Kinase [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A084.