Coagulation proteases modulate nucleic acid uptake and cGAS-STING-IFN induction in the tumor microenvironment.

ABSTRACT: Malignancies increase the risk for thrombosis and metastasis dependent on complex interactions of innate immune cells, platelets, and the coagulation system. Immunosuppressive functions of platelets and macrophage-derived coagulation factors in the tumor microenvironment (TME) drive tumor growth. Here, we show that patients with malignancies and tumor-bearing mice have increased levels of coagulation factor (F) X-expressing circulating monocytes engaged in platelet aggregate formation. This interaction and resulting thrombin generation on platelets interferes with monocyte differentiation and antigen uptake of antigen-presenting cells (APCs). Myeloid cell-specific deletion of FX or abrogated FXa signaling via protease activated receptor 2 (PAR2) averts the suppressive activity of platelets

SUBMITTER: Wilgenbus P 

PROVIDER: S-EPMC12487691 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature