Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Thromb Res. 2022 May;213 Suppl 1:S3-S7. doi: 10.1016/j.thromres.2021.12.013. Epub 2022 May 26.
Studies spanning the last 3 decades have fundamentally altered our understanding of the interplay between the hemostatic and immune systems. A plethora of studies have revealed that there is bidirectional crosstalk between these two systems at multiple levels that likely evolved as a means to coordinate the host response to numerous challenges, including trauma, infection, and thermal or chemical injury. Such challenges require reestablishment of vascular integrity, the clearance of pathogens, and removal of cellular and external debris. Clearly, bidirectional coordination of hemostasis and immunity would be beneficial in such contexts. Many types of malignancies take advantage of the interplay between hemostasis and immunity, co-opting these mechanisms to promote tumorigenesis, the formation of a supportive stroma, and metastasis to distant organs. Three important "bridges" that mechanistically link the hemostatic system to immune functions that have been shown to play a key role in cancer biology include the platelet/fibrinogen axis, protease activated receptor-1 (PAR-1) and protease activated receptor-2 (PAR-2). These hemostatic system components have been shown to regulate a variety of immune functions that support tumorigenesis in the context of inflammation-driven malignancy, metastasis, and escape from adaptive antitumor immunity. Understanding the mechanisms coupling these bridges between hemostasis and immunity, as well as others, could provide novel targets for the prevention and treatment of a variety of cancers.
跨越过去 30 年的研究从根本上改变了我们对止血和免疫系统之间相互作用的理解。大量研究揭示了这两个系统在多个层面上存在双向串扰，这可能是作为一种协调宿主对包括创伤、感染和热或化学损伤在内的多种挑战的反应的手段而进化的。这些挑战需要重建血管完整性，清除病原体，并清除细胞和外部碎片。显然，止血和免疫的双向协调在这种情况下是有益的。许多类型的恶性肿瘤利用止血和免疫之间的相互作用，利用这些机制促进肿瘤发生、支持性基质的形成以及转移到远处器官。已经表明，有三个重要的“桥梁”在机制上连接止血系统和免疫功能，它们在癌症生物学中起着关键作用，包括血小板/纤维蛋白原轴、蛋白酶激活受体-1 (PAR-1) 和蛋白酶激活受体-2 (PAR-2)。这些止血系统成分已被证明可以调节各种免疫功能，这些功能在炎症驱动的恶性肿瘤、转移和逃避适应性抗肿瘤免疫的情况下支持肿瘤发生。了解将止血和免疫联系起来的这些桥梁以及其他桥梁的机制，可能为预防和治疗各种癌症提供新的靶点。
