Platelets as regulators of anti-tumor immunity: mechanisms and clinical implications.

Abstract

Platelets are increasingly recognized as important contributors to tumor progression and metastatic dissemination. Platelets facilitate cancer cell survival, their safe transit through the hostile bloodstream, arrest at distant organ sites, and ultimate outgrowth into metastatic lesions. Although multiple platelet-dependent mechanisms have been implicated in cancer progression-including epithelial-mesenchymal transition and the provision of tumor-supportive growth factors-recent studies increasingly highlight immune modulation as a central mechanism underlying platelet-mediated metastasis. Accordingly, this review summarizes current evidence on the molecular and cellular mechanisms by which platelets regulate cytotoxic T lymphocyte and natural killer (NK) cell-mediated anti-tumor immune responses. Special attention is given to platelet-associated immune checkpoint pathways, including the expression and intercellular transfer of Programmed Death-Ligand 1 (PD-L1), as well as to the release of immunomodulatory mediators such as transforming growth factor-β1 (TGF-β1), thromboxane A₂ (TXA₂), and adenosine generated by platelet ectoenzymes. Finally, the potential implications of platelet-immune interactions for cancer therapy are discussed, with a particular focus on their relevance for immunotherapeutic strategies and metastatic disease control.