Abstract 620: Regulation of anti-tumor immune response by EphA2 receptor tyrosine kinase

Abstract

Abstract Eph receptors are the largest family of receptor tyrosine kinases. Overexpression of EphA2 is common across many types of human cancer, particularly in the late stage malignant diseases. We report here that EphA2 knock-out causes delayed tumor growth in several syngeneic mouse caner models, such as breast, colon, lung, and prostate cancer as well as melanoma. However, such effects are missing in immune deficient mice, which suggests the involvement of immune components. Immunophenotyping of the tumors shows elevated T cell infiltration and accompanied by reduced MDSC population in the EphA2 KO tumors. Single cell transcriptomic analysis and cytokine measurements support these results showing increased production of CCL5, CXCL9 and IFNg in the EphA2 KO tumors. Analysis on tumors at very early time points reveals elevated levels of CXCL1 and CXCL2 which recruits suppressive MDSCs. Consistently, 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 drive 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 micro- environment towards type I anti-tumor immune response. Citation Format: Roger Xiaojun Shi, Ryan Lingerak, So-Yeon Kim, Wei Wang, Khalid Sossey-Alaoui, Bingcheng Wang. Regulation of anti-tumor immune response by EphA2 receptor tyrosine kinase [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 620.