Predicting and Preventing Immune Checkpoint Inhibitor Toxicity: Targeting Cytokines

Jee Hye Kang; Jeffrey A Bluestone; Arabella Young

doi:10.1016/j.it.2021.02.006

Predicting and Preventing Immune Checkpoint Inhibitor Toxicity: Targeting Cytokines

Trends Immunol. 2021 Apr;42(4):293-311. doi: 10.1016/j.it.2021.02.006. Epub 2021 Mar 10.

Authors

Jee Hye Kang¹, Jeffrey A Bluestone², Arabella Young³

Affiliations

¹ Sean N. Parker Autoimmune Research Laboratory and Diabetes Center, University of California San Francisco, San Francisco, CA, USA.
² Sean N. Parker Autoimmune Research Laboratory and Diabetes Center, University of California San Francisco, San Francisco, CA, USA; Sonoma Biotherapeutics, South San Francisco, CA, USA.
³ Sean N. Parker Autoimmune Research Laboratory and Diabetes Center, University of California San Francisco, San Francisco, CA, USA; QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. Electronic address: arabella.young@ucsf.edu.

PMID: 33714688
DOI: 10.1016/j.it.2021.02.006

Abstract

Cancer immunotherapies can successfully activate immune responses towards certain tumors. However, this can also result in the development of treatment-induced immune-related adverse events (irAEs) in multiple tissues. Growing evidence suggests that cytokine production in response to these therapeutics potentiates the development of irAEs and may have predictive value as biomarkers for irAE occurrence. In addition, therapeutic agents that inhibit cytokine activity can limit the severity of irAEs, and their use is being tested in the clinical setting. This review provides an in-depth analysis of strategies to uncouple the cytokine response, that precipitates irAEs following cancer immunotherapies, from the benefit gained in promoting antitumor immunity.

Keywords: COVID-19; cytokines; immune checkpoint inhibitors; immune toxicity; immune-related adverse events; infliximab; interleukin; secukinumab; tocilizumab; tumor necrosis factor.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Cytokines*
Humans
Immune Checkpoint Inhibitors* / adverse effects
Immunotherapy / adverse effects
Neoplasms* / drug therapy

Substances

Cytokines
Immune Checkpoint Inhibitors

Grants and funding

K99 CA246061/CA/NCI NIH HHS/United States