Hemostasis and tumor immunity

Significant data have accumulated demonstrating a reciprocal relationship between cancer and the hemostatic system whereby cancer promotes life-threatening hemostatic system dysregulation (e.g., thromboembolism, consumptive coagulopathy), and hemostatic system components directly contribute to cancer pathogenesis. The mechanistic underpinnings of this relationship continue to be defined, but it is becoming increasingly clear that many of these mechanisms involve crosstalk between the hemostatic and immune systems. This is perhaps not surprising given that there is ample evidence for bidirectional crosstalk between the hemostatic and immune systems at multiple levels that likely evolved to coordinate the response to injury, host defense, and tissue repair. Much of the data linking hemostasis and immunity in cancer biology focus on innate immune system components. However, the advent of adaptive immunity-based cancer therapies such as immune checkpoint inhibitors has revealed that the relationship of hemostasis and immunity in cancer extends to the adaptive immune system. Adaptive immunity-based cancer therapies appear to be associated with an increased risk of thromboembolic complications, and hemostatic system components appear to regulate adaptive immune functions through diverse mechanisms to affect tumor progression. In this review, the evidence for crosstalk between hemostatic and adaptive immune system components is discussed, and the implications of this relationship in the context of cancer therapy are reviewed. A better understanding of these relationships will likely lead to strategies to make existing adaptive immune based therapies safer by decreasing thromboembolic risk and may also lead to novel targets to improve adaptive immune-based cancer treatments.