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| 001 | 304484 | ||
| 005 | 20250914022649.0 | ||
| 024 | 7 | _ | |a 10.1172/jci.insight.190311 |2 doi |
| 024 | 7 | _ | |a pmid:40694429 |2 pmid |
| 024 | 7 | _ | |a altmetric:181350593 |2 altmetric |
| 037 | _ | _ | |a DKFZ-2025-01876 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Wilgenbus, Petra |b 0 |
| 245 | _ | _ | |a Coagulation proteases modulate nucleic acid uptake and cGAS-STING-IFN induction in the tumor microenvironment. |
| 260 | _ | _ | |a Ann Arbor, Michigan |c 2025 |b JCI Insight |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1757570380_26504 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a 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. |
| 536 | _ | _ | |a 899 - ohne Topic (POF4-899) |0 G:(DE-HGF)POF4-899 |c POF4-899 |f POF IV |x 0 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de |
| 650 | _ | 7 | |a Cancer immunotherapy |2 Other |
| 650 | _ | 7 | |a Coagulation |2 Other |
| 650 | _ | 7 | |a Immunology |2 Other |
| 650 | _ | 7 | |a Oncology |2 Other |
| 650 | _ | 7 | |a Platelets |2 Other |
| 650 | _ | 7 | |a Vascular biology |2 Other |
| 650 | _ | 7 | |a Membrane Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a Nucleotidyltransferases |0 EC 2.7.7.- |2 NLM Chemicals |
| 650 | _ | 7 | |a STING1 protein, human |2 NLM Chemicals |
| 650 | _ | 7 | |a cGAS protein, human |0 EC 2.7.7.- |2 NLM Chemicals |
| 650 | _ | 7 | |a Sting1 protein, mouse |2 NLM Chemicals |
| 650 | _ | 7 | |a Factor Xa |0 EC 3.4.21.6 |2 NLM Chemicals |
| 650 | _ | 7 | |a Receptor, PAR-2 |2 NLM Chemicals |
| 650 | _ | 7 | |a cGAS protein, mouse |0 EC 2.7.7.- |2 NLM Chemicals |
| 650 | _ | 2 | |a Tumor Microenvironment: immunology |2 MeSH |
| 650 | _ | 2 | |a Animals |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Mice |2 MeSH |
| 650 | _ | 2 | |a Membrane Proteins: metabolism |2 MeSH |
| 650 | _ | 2 | |a Nucleotidyltransferases: metabolism |2 MeSH |
| 650 | _ | 2 | |a Neoplasms: immunology |2 MeSH |
| 650 | _ | 2 | |a Neoplasms: pathology |2 MeSH |
| 650 | _ | 2 | |a Signal Transduction |2 MeSH |
| 650 | _ | 2 | |a Blood Platelets: metabolism |2 MeSH |
| 650 | _ | 2 | |a Blood Platelets: immunology |2 MeSH |
| 650 | _ | 2 | |a Factor Xa: metabolism |2 MeSH |
| 650 | _ | 2 | |a Factor Xa: genetics |2 MeSH |
| 650 | _ | 2 | |a Female |2 MeSH |
| 650 | _ | 2 | |a Receptor, PAR-2: metabolism |2 MeSH |
| 650 | _ | 2 | |a Receptor, PAR-2: genetics |2 MeSH |
| 650 | _ | 2 | |a CD8-Positive T-Lymphocytes: immunology |2 MeSH |
| 650 | _ | 2 | |a Mice, Inbred C57BL |2 MeSH |
| 650 | _ | 2 | |a Monocytes: metabolism |2 MeSH |
| 650 | _ | 2 | |a Monocytes: immunology |2 MeSH |
| 650 | _ | 2 | |a Antigen-Presenting Cells: immunology |2 MeSH |
| 650 | _ | 2 | |a Male |2 MeSH |
| 700 | 1 | _ | |a Pott, Jennifer |b 1 |
| 700 | 1 | _ | |a Pagel, Sven |b 2 |
| 700 | 1 | _ | |a Witzler, Claudius |b 3 |
| 700 | 1 | _ | |a Royce, Jennifer |b 4 |
| 700 | 1 | _ | |a Marini, Federico |b 5 |
| 700 | 1 | _ | |a Reyda, Sabine |b 6 |
| 700 | 1 | _ | |a Madhusudhan, Thati |b 7 |
| 700 | 1 | _ | |a Kindler, Thomas |0 P:(DE-HGF)0 |b 8 |
| 700 | 1 | _ | |a Hausen, Anne |b 9 |
| 700 | 1 | _ | |a Gaida, Matthias M |b 10 |
| 700 | 1 | _ | |a Weiler, Hartmut |b 11 |
| 700 | 1 | _ | |a Ruf, Wolfram |b 12 |
| 700 | 1 | _ | |a Graf, Claudine |b 13 |
| 773 | _ | _ | |a 10.1172/jci.insight.190311 |g Vol. 10, no. 17, p. e190311 |0 PERI:(DE-600)2874757-4 |n 17 |p e190311 |t JCI insight |v 10 |y 2025 |x 2379-3708 |
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