The Angiocrine Niche in Cancer Therapy Responses: The Role of Vascular Endothelial Cells in Immunomodulation

Vascular endothelial cells (ECs) within the tumor microenvironment (TME) function as active signaling hubs, not just passive conduits for nutrients. They secrete angiocrine factors that regulate cancer growth, metastasis, and response to therapy. These cells, specifically immunomodulatory ECs (iMECs), act as immune gatekeepers by directly interacting with and influencing immune cell function. This review examines how the angiocrine niche contributes to therapeutic resistance by modulating the immune landscape. We delineate key iMEC states that dictate the TME's immunological state, from an immune-responsive hot niche to a treatment-resistant cold state. These phenotypes include signatures that facilitate lymphocyte homing (HEV-like), recruit effector T cells (IFN-like), enable antigen presentation, and secrete distinct chemokine and cytokine profiles. Furthermore, we discuss how therapeutic interventions can induce EC senescence and alter angiocrine signals, thereby promoting therapy resistance. Understanding these complex EC–immune interactions is crucial for developing novel strategies to target the angiocrine axis and improve patient outcomes.