Advances on immune-related adverse events associated with immune checkpoint inhibitors

Abstract

Immunotherapy has recently led to a paradigm shift in cancer therapy, in which immune checkpoint inhibitors (ICIs) are the most successful agents approved for multiple advanced malignancies. However, given the nature of the non-specific activation of effector T cells, ICIs are remarkably associated with a substantial risk of immune-related adverse events (irAEs) in almost all organs or systems. Up to 90% of patients who received ICIs combination therapy experienced irAEs, of which majority were low-grade toxicity. Cytotoxic lymphocyte antigen-4 and programmed cell death protein-1/programmed cell death ligand 1 inhibitors usually display distinct features of irAEs. In this review, the mechanisms of action of ICIs and how they may cause irAEs are described. Some unsolved challenges, however really engrossing issues, such as the association between irAEs and cancer treatment response, tumor response to irAEs therapy, and ICIs in challenging populations, are comprehensively summarized.

Keywords

cancer / immunotherapy / immune checkpoint inhibitors / immune-related adverse events / review

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Acknowledgements

This work was supported by the Beijing Natural Science Foundation (No.7184251) and National Natural Science Foundation of China (Nos. 91442120 and 81771740).

Compliance with ethics guidelines

Yong Fan, Yan Geng, Lin Shen, and Zhuoli Zhang declare that they have no financial conflicts of interest. This manuscript is a review article and does not involve a research protocol requiring approval by a relevant institutional review board or ethics committee.

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