Cancer patients treated with immune checkpoint inhibitors have a high risk of developing blood clots (thrombosis). Immune checkpoint inhibitors are new drugs that allow activation of the immune system so that it can attack cancer cells. However, the immune activation cannot specifically target cancer cells and normal organs can be affected. We believe that the blood clots that develop in patients treated with immune checkpoint inhibitors are a results of inflammation leading to damage and/or activation of normal vascular cells, including platelets. Our preliminary data suggest that immune checkpoint inhibitors may enhance platelet activation, and that activated platelets shed some of the target proteins of the immune checkpoint inhibitors. We hypothesize that these targets may be transferred to other cells that are in turn targeted by immune checkpoint inhibitors. Once activated, these cells may contribute to thrombosis.
Immune checkpoint inhibitors provide a new approach to treating cancer, by harnessing the power of the immune system to attack tumors. However, activation of the immune system may also cause side effects, one of which appears to be an increased risk of blood clots. This project will focus on the mechanisms underlying this important side effect, particularly the role of blood platelets.