Antigen Presentation by Tumor Endothelium Promotes CD8+ T Cell Recruitment 2259470

Abstract

Abstract Introduction The endothelium, traditionally considered a physical barrier between blood and tissues, is increasingly recognized for its potential role in modulating immune responses. Preclinical models have shown that inhibiting tumor angiogenesis enhances CD8+ T cell infiltration and upregulates antigen presentation and processing pathways in tumor endothelial cells, suggesting that endothelial cells may play an active role in shaping tumor immunity. Methods In this study, we investigated the immunoregulatory role of tumor endothelial cells by examining their ability to present antigens using endothelial cell-specific beta 2-microglobulin (B2m) or IFN-gamma receptor (Ifngr1) knockout mice in three tumor models. Results We showed that tumor endothelial cells can present tumor-derived antigens via MHC-I to naive CD8+ T cells, upregulating lymphocyte function-associated antigen-1 (LFA-1) and facilitating their trans-endothelial migration into tumors. This process requires beta 2-microglobulin (B2m) and IFN-gamma signaling in endothelial cells, as deleting these molecules reduces CD8+ T cell recruitment and exacerbates tumor growth. Moreover, combining anti-angiogenic and anti-PD1 therapy boosts endothelial antigen presentation and increases stem-like, antigen-specific CD8+ T cells within the tumor. Conclusion These findings identify endothelial antigen presentation as a critical mechanism that links tumor vasculature and T cell immunity, providing a promising avenue to enhance immunotherapy efficacy. Funding Source n/a Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)