Hemostasis and tumor immunity

Abstract

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.

Reprogramming the immunosuppressive tumor microenvironment: exploiting angiogenesis and thrombosis to enhance immunotherapy

“…Many cancer patients also display elevated serum levels of platelet-derived EVs and p-selectin in their serum, indicating systemic platelet activation. Tumor cell-induced platelet activation (TCIPA) involves multiple mechanisms ( 110 – 112 ). For example, the glycoprotein podoplanin (PDPN) expressed on the surface of many tumor cells binds the C-type lectin receptor-2 (CLEC-2) on the platelets leading to platelet aggregation and thrombus formation ( 113 – 115 ).…”

Nanomaterials augmented bioeffects of ultrasound in cancer immunotherapy

“…Immunotherapy, which aims to eliminate tumor cells by unleashing the host immune system rather than directly killing them, is a monumental breakthrough in cancer treatment that has revolutionized cancer treatment protocols [ 20 ]. The innate and adaptive immune systems, including T cells, dendritic cells (DCs), macrophages, natural killer (NK) cells and B cells, contribute to tumor progression and immune response [ [21] , [22] , [23] ]. Effective immune response can alter tumor phenotype and impair cell function, and even eradicate tumor cells, which is not only effective against primary and distant tumors, but also effectively prevents tumor recurrence through immune memory effects [ 24 ].…”

The Crossroads of the Coagulation System and the Immune System: Interactions and Connections

“…Emerging evidence suggests that dysregulated coagulation may contribute to the pathogenesis of autoimmune diseases, cancer, and chronic inflammatory disorders. Conversely, immune dysregulation may promote a prothrombotic state, increasing the risk of venous and arterial thrombosis [ 15 , 16 , 17 , 18 ].…”