Cantrell Rachel, Palumbo Joseph S
Cancer and Blood Diseases Institute Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine Cincinnati Ohio USA.
Res Pract Thromb Haemost. 2022 May 25;6(4):e12728. doi: 10.1002/rth2.12728. eCollection 2022 May.
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.
大量数据已积累起来，表明癌症与止血系统之间存在一种相互关系，即癌症会促进危及生命的止血系统失调（如血栓栓塞、消耗性凝血病），而止血系统成分直接促成癌症发病机制。这种关系的机制基础仍在不断明确，但越来越清楚的是，其中许多机制涉及止血系统与免疫系统之间的相互作用。鉴于有充分证据表明止血系统与免疫系统在多个层面存在双向相互作用，这可能并不令人惊讶，这种相互作用可能是为了协调对损伤、宿主防御和组织修复的反应而进化而来的。癌症生物学中许多将止血与免疫联系起来的数据都集中在先天免疫系统成分上。然而，基于适应性免疫的癌症疗法（如免疫检查点抑制剂）的出现表明，癌症中止血与免疫的关系延伸到了适应性免疫系统。基于适应性免疫的癌症疗法似乎与血栓栓塞并发症风险增加有关，并且止血系统成分似乎通过多种机制调节适应性免疫功能以影响肿瘤进展。在这篇综述中，我们讨论了止血系统与适应性免疫系统成分之间相互作用的证据，并综述了这种关系在癌症治疗背景下的意义。更好地理解这些关系可能会带来一些策略，通过降低血栓栓塞风险使现有的基于适应性免疫的疗法更安全，也可能会带来新的靶点以改善基于适应性免疫的癌症治疗。
