Review Article

Cancer immune checkpoint blockade therapy and its associated autoimmune cardiotoxicity

Authors: Jiu-cheng Zhang1, Wei-dong Chen1, Jean Bustamante Alvarez2, Kelly Jia2, Lei Shi3, Qiang Wang3, Ning Zou1, Kai He2, Hua Zhu3
1 Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan 430079, China
2 Department of Internal Medicine, The Ohio State University Wexner Medical Center and James Cancer Hospital, Columbus, Ohio 43210, USA
3 Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio 43210, USA
Correspondence to: Ning Zou: sunnyning116@163.com, Kai He: kai.he@osumc.edu, Hua Zhu: Hua.Zhu@osumc.edu,
DOI: 10.1038/s41401-018-0062-2
Received: 31 March 2018
Accepted: 5 June 2018
Advance online: 10 July 2018

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.
Keywords: cancer immunotherapy; immune checkpoint inhibitor; CTLA-4; PD-1; PD-L1; cardiac toxicity; myocarditis

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