Blood coagulation and cancer are intrinsically connected, hypercoagulation-associated thrombotic complications are commonly observed in certain types of cancer, often leading to decreased survival in cancer patients. Apart from the common role in coagulation, coagulation proteases often trigger intracellular signaling in various cancers via the activation of a G protein-coupled receptor superfamily protease: protease-activated receptors (PARs). Although the role of PARs is well-established in the development and progression of certain types of cancer, their impact on cancer immune response is only just emerging. The present review highlights how coagulation protease-driven PAR signaling plays a key role in modulating innate and adaptive immune responses. This is followed by a detailed discussion on the contribution of coagulation protease-induced signaling in cancer immune evasion, thereby supporting the growth and development of certain tumors. A special section of the review demonstrates the role of coagulation proteases, thrombin, factor VIIa, and factor Xa in cancer immune evasion. Targeting coagulation protease-induced signaling might be a potential therapeutic strategy to boost the immune surveillance mechanism of a host fighting against cancer, thereby augmenting the clinical consequences of targeted immunotherapeutic regimens.
凝血与癌症之间存在内在联系，某些类型癌症中常观察到高凝状态相关的血栓并发症，这往往导致癌症患者生存率降低。除了在凝血过程中的常见作用外，凝血蛋白酶还经常通过激活G蛋白偶联受体超家族蛋白酶——蛋白酶激活受体（PARs），在多种癌症中触发细胞内信号传导。尽管PARs在某些癌症的发生和发展中的作用已得到充分证实，但它们对癌症免疫反应的影响才刚刚显现。本综述重点阐述了凝血蛋白酶驱动的PAR信号传导如何在调节先天性和适应性免疫反应中发挥关键作用。随后详细讨论了凝血蛋白酶诱导的信号传导在癌症免疫逃逸中的作用，从而支持某些肿瘤的生长和发展。综述的一个专门部分展示了凝血蛋白酶、凝血酶、因子VIIa和因子Xa在癌症免疫逃逸中的作用。靶向凝血蛋白酶诱导的信号传导可能是一种潜在的治疗策略，可增强宿主对抗癌症的免疫监视机制，从而改善靶向免疫治疗方案的临床效果。
Coagulation Protease-Driven Cancer Immune Evasion: Potential Targets for Cancer Immunotherapy
肿瘤(癌症)患者之家