Cancer immune checkpoint blockade therapy and its associated autoimmune cardiotoxicity. (November 2018)

• Record Type: Journal Article
• Authors: Zhang, Jiu-cheng; Chen, Wei-dong; Alvarez, Jean; Jia, Kelly; Shi, Lei; Wang, Qiang; Zou, Ning; He, Kai; Zhu, Hua
• Is Part Of: Acta pharmacologica Sinica. Volume 39:Number 11(2018)
• Page Start: 1693
• Page End: 1698
• Publication Date: 2018-11
• Subjects: cancer immunotherapy -- immune checkpoint inhibitor -- CTLA-4 -- PD-1 -- PD-L1 -- cardiac toxicity -- myocarditis; Pharmacology -- Periodicals; 615.105
• DOI: 10.1038/s41401-018-0062-2
• Languages: English
• ISSNs: 1671-4083

Abstract

Abstract The immune checkpoint molecules are emerged in the evolution to protect the host from self-attacks by activated T cells. However, cancer cells, as a strategy to survive and expand, can hijack these molecules and mechanisms to suppress T cell-mediated immune responses. Therefore, an idea of blocking the checkpoint molecules to enhance the anti-tumor activities of the host immune system has been developed and applied to the cancer therapy after discovery of the inhibitory T cell co-receptor, cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and further enhanced on the identification of PD-1 and its ligands. Since 2010, several checkpoint inhibitors have been approved by FDA and many more are in clinical trials. In the treatment of advanced cancers, these inhibitors significantly increased response rates and survival benefits. However, accompanied with the striking results, immune-related adverse events (irAEs) that broadly occurred in many organs were observed and reported, some of which were fatal. Herein, we first review the recent progressions in the research of the immune checkpoint molecules and the application of their blocking antibodies in cancer treatment, and then discuss the cardiac toxicity induced by the therapy and the strategy to monitor, manage this adverse event when it occurs.