Tumor Endothelial ITGA5 Expression Induces T cell Dysfunction in Cervical Cancer

Tumor vascular endothelial cells (TVECs), which originate from normal vascular endothelial cells surrounding the tumor, play a critical role in shaping the immunosuppressive tumor microenvironment and contributing to resistance to immunotherapy in cervical cancer. However, the molecular mechanisms underlying TVEC-mediated regulation of anti-tumor immunity remain elusive. Here, we performed a comprehensive assessment of integrin family proteins in cervical cancer-derived TVECs and identified ITGA5 as a key regulator of T cell activity within the tumor microenvironment. Loss of ITGA5 in TVECs markedly enhanced antigen presentation by upregulating both MHC class I and class II pathways, thereby promoting T cell activation and cytotoxic function. Importantly, therapeutic blockade of ITGA5 significantly enhanced the efficacy of anti–PD-1 treatment, and the combination of ITGA5 antibody and PD-1 blockade synergistically inhibited tumor growth in orthotopic murine models. Collectively, these findings identify ITGA5 as a previously unrecognized immune regulator in tumor vasculature and suggest that targeting endothelial ITGA5 may represent a promising strategy to improve immunotherapy efficacy in cervical cancer.