Myeloid cell-synthesized coagulation factor X dampens antitumor immunity
Related Experiment Video
Updated: Jan 19, 2026
Development of an Insert Co-culture System of Two Cellular Types in the Absence of Cell-Cell Contact
Published on: July 17, 2016
Claudine Graf1,2,3, Petra Wilgenbus1, Sven Pagel1
1Center for Thrombosis and Hemostasis, Johannes Gutenberg University Medical Center, Mainz, Germany.
Abstract:
Immune evasion in the tumor microenvironment (TME) is a crucial barrier for effective cancer therapy, and plasticity of innate immune cells may contribute to failures of targeted immunotherapies. Here, we show that rivaroxaban, a direct inhibitor of activated coagulation factor X (FX), promotes antitumor immunity by enhancing infiltration of dendritic cells and cytotoxic T cells at the tumor site. Profiling FX expression in the TME identifies monocytes and macrophages as crucial sources of extravascular FX. By generating mice with immune cells lacking the ability to produce FX, we show that myeloid cell-derived FX plays a pivotal role in promoting tumor immune evasion. In mouse models of cancer, we report that the efficacy of rivaroxaban is comparable with anti-programmed cell death ligand 1 (PD-L1) therapy and that rivaroxaban synergizes with anti-PD-L1 in improving antitumor immunity. Mechanistically, we demonstrate that FXa promotes immune evasion by signaling through protease-activated receptor 2 and that rivaroxaban specifically targets this cell-autonomous signaling pathway to reprogram tumor-associated macrophages. Collectively, our results have uncovered the importance of FX produced in the TME as a regulator of immune cell activation and suggest translational potential of direct oral anticoagulants to remove persisting roadblocks for immunotherapy and provide extravascular benefits in other diseases.
Insights
Rivaroxaban, an inhibitor of coagulation factor X (FX), enhances antitumor immunity by improving immune cell infiltration into tumors. This drug synergizes with anti-PD-L1 therapy, offering a new strategy against cancer immune evasion.
Area of Science:
- Immunology
- Oncology
- Hematology
Background:
- Immune evasion within the tumor microenvironment (TME) hinders effective cancer immunotherapy.
- Innate immune cell plasticity can lead to targeted immunotherapies failing.
Purpose of the Study:
- To investigate the role of coagulation factor X (FX) in tumor immune evasion.
- To evaluate rivaroxaban, a direct FX inhibitor, as a potential immunotherapy enhancer.
Main Methods:
- Profiling FX expression in the TME of mouse cancer models.
- Generating genetically modified mice lacking FX production in immune cells.
- Assessing the efficacy of rivaroxaban alone and in combination with anti-PD-L1 therapy.
- Investigating the mechanism of FXa-mediated immune evasion via protease-activated receptor 2 (PAR2) signaling.
Main Results:
- FX is primarily expressed by monocytes and macrophages in the TME.
- Myeloid cell-derived FX significantly contributes to tumor immune evasion.
- Rivaroxaban enhances dendritic cell and cytotoxic T cell infiltration into tumors.
- Rivaroxaban demonstrates comparable efficacy to anti-PD-L1 therapy and synergizes with it.
- FXa signals through PAR2 to promote immune evasion by reprogramming tumor-associated macrophages.
Conclusions:
- FX produced within the TME is a critical regulator of immune cell activity and promotes immune evasion.
- Rivaroxaban effectively targets the FXa/PAR2 pathway, reprogramming tumor-associated macrophages and enhancing antitumor immunity.
- Direct oral anticoagulants like rivaroxaban hold translational potential for overcoming immunotherapy resistance and may benefit other diseases with extravascular components.
More Related Videos
10:21Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
Published on: February 21, 2018
09:57Real Time Detection of In Vitro Tumor Cell Apoptosis Induced by CD8+ T Cells to Study Immune Suppressive Functions of Tumor-infiltrating Myeloid Cells
Published on: January 29, 2019
Related Concept Videos
01:01Regulation of Hematopoietic Stem Cells
01:15Differentiation of Common Myeloid Progenitor Cells
02:23Abnormal Proliferation
01:27Tumor Immunotherapy