[The Svedberg seminar] – Coagulation: Cancer’s new best friend

Gareth Owen

Professor Pontificia Universidad Católica de Chile, Chile

Bio

Dr. Gareth Owen is currently visiting Professor in the lab of Dr Masood Kamali-Moghaddam, Department of Immunology, Genetics and Pathology, Uppsala University. He is a full professor in the Faculty of Biological Sciences and Faculty of Medicine at the Pontificia Universidad Catolica de Chile. Dr Owen did his BSc at King’s College London and has a PhD from the Royal Postgraduate Medical School, Hammersmith Hospital, London UK (Imperial College London).  This was followed by a post-doctoral fellowships at the University of Colorado USA, and the Institute of Cancer Research (ICR-UK). Dr Owen is a PI in the Millennium Institute on Immunology and Immunotherapy Chile, and Board member of the Chilean National Cancer Forum.

Coagulation: Cancer’s new best friend

Coagulation is linked to cancer progression, with many patients exhibiting chronic hypercoagulability. Anticoagulant therapy has been associated with improved outcomes. Beyond hemostasis, the coagulation system can drive inflammation and metastasis, though the mechanisms remain unclear. Herein, we demonstrate that elevated levels of activated coagulation factor X (FXa) increase lung metastasis and that FXa promotes an immunosuppressive tumor microenvironment. Using a murine model of melanoma and in vitro assays, we found that FXa increased infiltration of regulatory T cells and Th17 cells, and upregulated PD-1 and CTLA-4 expression on CD4+ and CD8+ T cells. Co-treatment with the anti-FXa anticoagulant dalteparin abrogated these effects. Mechanistically, FXa in vitro suppressed macrophage M1 and Th1 differentiation through the Protease-Activated Receptor-1 (PAR1). The clinically approved PAR1 inhibitor Vorapaxar blocked FXa-induced tumor progression in vivo. These findings identify FXa or PAR1 inhibition as therapeutic strategies in cancer therapy.

Host: Masood Kamali-Moghaddam masood.kamali@igp.uu.se, UU

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