Understanding adverse events of immunotherapy: A mechanistic perspective
Open Access
- 18 December 2020
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 218 (1)
- https://doi.org/10.1084/jem.20192179
Abstract
The treatment of many cancers has been revolutionized by immune checkpoint blockade (ICB) as a standard-of-care therapeutic. Despite many successes, a large proportion of patients treated with ICB agents experience immune-related adverse events (irAEs) in the form of clinical autoimmunity, ranging from mild to life threatening, that can limit cancer treatment. A mechanistic understanding of these irAEs is required to better treat or prevent irAEs and to predict those patients who are susceptible to irAEs. We propose several mechanisms that may contribute to the generation of irAEs: (1) preexisting susceptibility to autoimmunity, (2) aberrant presentation of “self” by the tumor, and (3) loss of tolerance driven by the tumor or tissue microenvironment.Keywords
Funding Information
- National Institutes of Health (F31 AI147638, T32 AI089443, T32 HL116324, P01 AI108545, R01 DK089125, P50 CA127003)
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