Delgobo Murilo, Frantz Stefan
Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany.
Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.
J Thorac Dis. 2018 Dec;10(Suppl 35):S4323-S4334. doi: 10.21037/jtd.2018.10.07.
The introduction of immune checkpoint inhibitors have greatly improved clinical outcomes in several cancer types, revolutionizing the management of a wide variety of tumors endowed with poor prognosis. Despite its success, high grade immune related adverse events were observed in patients treated with checkpoint inhibitors. While cardiotoxicity was largely underestimated in initial studies, numerous reports of fulminant myocarditis and fatal heart failure (HF) have been recently described. In this review we discuss possible mechanisms involved in cardiac toxicity triggered by inhibition of cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) pathway, the most prominent checkpoint inhibitors available in the clinic. Major cardiovascular events associated with checkpoint inhibitors adds another layer of complexity in cancer therapy and urges for an interdisciplinary approach between oncologists, cardiologists, and immunologist.
免疫检查点抑制剂的引入极大地改善了几种癌症类型的临床结局,彻底改变了对多种预后不良肿瘤的治疗方式。尽管取得了成功,但在接受检查点抑制剂治疗的患者中观察到了高级别免疫相关不良事件。虽然心脏毒性在最初的研究中被大大低估,但最近已有许多暴发性心肌炎和致命心力衰竭(HF)的报道。在这篇综述中,我们讨论了由抑制细胞毒性T淋巴细胞抗原4(CTLA-4)和程序性细胞死亡1(PD-1)通路引发心脏毒性的可能机制,这是临床上最突出的检查点抑制剂。与检查点抑制剂相关的主要心血管事件给癌症治疗增加了另一层复杂性,并促使肿瘤学家、心脏病学家和免疫学家采取跨学科方法。