Tumor-associated endothelial cells in tumor immune escape and immunotherapy: multifaceted roles and treatment approaches

The tumor microenvironment (TME) is a key factor influencing carcinogenesis, disease progression, and therapeutic outcomes. Tumor-associated endothelial cells (TECs), integral components of the TME, form the structural and functional foundation of the vasculature, while also modulating tumor immune responses. TECs regulate immune cell activity and distribution through multiple molecular mechanisms, thereby influencing tumor immunity. Recent evidence highlights TEC-targeted interventions as a promising strategy to enhance immunotherapy efficacy. This review examines the mechanisms through which TECs drive tumorigenesis, progression, and metastasis, and explores the therapeutic potential of TEC-targeted approaches in cancer treatment. It also provides a systematic analysis of TECs’ impact on the immune microenvironment, assessing the potential of TEC-directed therapies to overcome chemoresistance and immunotherapy resistance, thus offering new perspectives for drug development targeting TECs. Finally, the review critically evaluates potential molecular targets within TECs and recent advancements in genetic research for cancer therapy, emphasizing key research priorities and pressing clinical challenges that require urgent focus.