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Orthogonal validation in an external placebo cohort from a phase 3 trial confirmed the model\u2019s predictive power. Further investigation into the mechanistic role of CD200 receptor 1 (CD200R1), an immune checkpoint receptor known to limit leukocyte inflammatory response that contributed strongly to the model, showed that reduced concentrations in plasma correlated with higher D-dimer concentrations and thrombosis risk. CD200R1-deficient mice were characterized by features of a prothrombotic state, with elevated thrombin-antithrombin complexes, increased interleukin-17A (IL-17A), and endothelial inflammation. Administration of anti\u2013IL-17A antibodies to CD200R1-deficient mice normalized thrombin-antithrombin complexes in vivo, and a meta-analysis of human COVID-19 studies showed reduced pulmonary thromboembolism in those on anti\u2013IL-17A antibodies. These findings highlight the utility of plasma proteomics to improve prediction of thrombosis in patients with cancer and to identify unanticipated mechanistic insights and therapeutic targets in thrombo-inflammatory disease.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adu7160","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:58:46Z","timestamp":1781719126000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Plasma proteomics improves thrombosis prediction in patients with cancer and identifies targetable IL-17\u2013driven endothelial activation"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3961-3399","authenticated-orcid":true,"given":"Dimitra","family":"Karagkouni","sequence":"first","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA."},{"name":"Broad Institute of 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