% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Wilgenbus:304484,
      author       = {P. Wilgenbus and J. Pott and S. Pagel and C. Witzler and J.
                      Royce and F. Marini and S. Reyda and T. Madhusudhan and T.
                      Kindler$^*$ and A. Hausen and M. M. Gaida and H. Weiler and
                      W. Ruf and C. Graf},
      title        = {{C}oagulation proteases modulate nucleic acid uptake and
                      c{GAS}-{STING}-{IFN} induction in the tumor
                      microenvironment.},
      journal      = {JCI insight},
      volume       = {10},
      number       = {17},
      issn         = {2379-3708},
      address      = {Ann Arbor, Michigan},
      publisher    = {JCI Insight},
      reportid     = {DKFZ-2025-01876},
      pages        = {e190311},
      year         = {2025},
      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 on tumor
                      cell debris uptake and promotes the immune stimulatory
                      activity of APCs in the TME. Myeloid cell FXa-PAR2 signaling
                      deficiency specifically enhances activation of the
                      cGAS-STING-IFN-I pathway with a resulting expansion of
                      antigen experienced progenitor exhausted CD8+ T cells.
                      Pharmacological blockade of FXa with direct oral
                      anticoagulants expands T cell priming-competent immune cells
                      in the TME and synergizes with the reactivation of exhausted
                      CD8+ T cells by immune checkpoint inhibitors for improved
                      antitumor responses. These data provide mechanistic insights
                      into the emerging clinical evidence demonstrating the
                      translational potential of FXa inhibition to synergize with
                      immunotherapy.},
      keywords     = {Tumor Microenvironment: immunology / Animals / Humans /
                      Mice / Membrane Proteins: metabolism /
                      Nucleotidyltransferases: metabolism / Neoplasms: immunology
                      / Neoplasms: pathology / Signal Transduction / Blood
                      Platelets: metabolism / Blood Platelets: immunology / Factor
                      Xa: metabolism / Factor Xa: genetics / Female / Receptor,
                      PAR-2: metabolism / Receptor, PAR-2: genetics / CD8-Positive
                      T-Lymphocytes: immunology / Mice, Inbred C57BL / Monocytes:
                      metabolism / Monocytes: immunology / Antigen-Presenting
                      Cells: immunology / Male / Cancer immunotherapy (Other) /
                      Coagulation (Other) / Immunology (Other) / Oncology (Other)
                      / Platelets (Other) / Vascular biology (Other) / Membrane
                      Proteins (NLM Chemicals) / Nucleotidyltransferases (NLM
                      Chemicals) / STING1 protein, human (NLM Chemicals) / cGAS
                      protein, human (NLM Chemicals) / Sting1 protein, mouse (NLM
                      Chemicals) / Factor Xa (NLM Chemicals) / Receptor, PAR-2
                      (NLM Chemicals) / cGAS protein, mouse (NLM Chemicals)},
      cin          = {FM01},
      ddc          = {610},
      cid          = {I:(DE-He78)FM01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40694429},
      doi          = {10.1172/jci.insight.190311},
      url          = {https://inrepo02.dkfz.de/record/304484},
}