4.7 Review

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

Journal

FRONTIERS OF MEDICINE
Volume 15, Issue 1, Pages 33-42

Publisher

SPRINGER
DOI: 10.1007/s11684-019-0735-3

Keywords

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

Funding

  1. Beijing Natural Science Foundation [7184251]
  2. National Natural Science Foundation of China [91442120, 81771740]

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Immunotherapy has revolutionized cancer treatment, with immune checkpoint inhibitors being the most successful agents, but they come with a risk of immune-related adverse events. The mechanisms of ICIs and irAEs have been discussed, and the comprehensive summary focuses on unresolved challenges and intriguing issues in this field.
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.

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