Coagulation signaling and cancer immunotherapy.
|
| Abstract |
The last decades have delineated many interactions of the hemostatic system with cancer cells that are pivotal for cancer-associated thrombosis, angiogenesis and metastasis. Expanding evidence shows that platelets, the tissue factor pathway, and proteolytic signaling involving protease-activated receptors (PARs) are also central players in innate and adaptive immunity. Recent studies in immune-competent mice have uncovered new immune-evasive roles of coagulation signaling networks in the development and growth of different preclinical tumor models. Tumor-type specific PAR1 signaling facilitates the escape from immune surveillance by cytotoxic T cells. In addition, tumor-associated macrophages produce factor X (FX) and cell autonomous FXa-PAR2 signaling emerges as a central mechanism for tumor-promoting macrophage polarization in the tumor microenvironment. Pharmacological targeting of this signaling pathway with tissue penetrating oral FXa inhibitor reprograms macrophage phenotypes, enhances tumor antigen presentation, and expands tumor-killing cytotoxic lymphocytes. Importantly, by specifically targeting innate immune cells, the oral FXa inhibitor rivaroxaban synergizes with checkpoint inhibitor therapy in enhancing antigen-specific antitumor immunity. In similar experiments, anticoagulation with heparin is inefficient to block extravascular coagulation signaling. Thus, antithrombotic therapy with oral FXa inhibitors may contribute to reversing tumor immune-evasive mechanisms and enhance the clinical outcome of targeted immuno-therapy regimens.
|
|---|---|
| Authors | Wolfram Ruf, Claudine Graf |
| Journal | Thrombosis research (Thromb Res) Vol. 191 Suppl 1 Pg. S106-S111 (07 2020) ISSN: 1879-2472 [Electronic] United States |
| PMID | 32736766 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | © 2020 Elsevier Ltd. All rights reserved. |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!