Postdoc research associate Washington Univ. Sch. of Med., St. Louis, United States
Disclosure(s):
Yoojung Kwon, PhD: No financial relationships to disclose
Introduction/Rationale: 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.
