CD4 T cells and toxicity from immune checkpoint blockade.
immune checkpoint inhibitors
immune-related adverse events
immunotherapy
irAEs
melanoma
predictive biomarkers
Journal
Immunological reviews
ISSN: 1600-065X
Titre abrégé: Immunol Rev
Pays: England
ID NLM: 7702118
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
15
04
2023
accepted:
27
06
2023
medline:
25
9
2023
pubmed:
26
7
2023
entrez:
26
7
2023
Statut:
ppublish
Résumé
Immune-related toxicities, otherwise known as immune-related adverse events (irAEs), occur in a substantial fraction of cancer patients treated with immune checkpoint inhibitors (ICIs). Ranging from asymptomatic to life-threatening, ICI-induced irAEs can result in hospital admission, high-dose corticosteroid treatment, ICI discontinuation, and in some cases, death. A deeper understanding of the factors underpinning severe irAE development will be essential for improved irAE prediction and prevention, toward maximizing the benefits and safety profiles of ICIs. In recent work, we applied mass cytometry, single-cell RNA sequencing, single-cell V(D)J sequencing, bulk RNA sequencing, and bulk T-cell receptor (TCR) sequencing to identify pretreatment determinants of severe irAE development in patients with advanced melanoma. Across 71 patients separated into three cohorts, we found that two baseline features in circulation-elevated activated CD4 effector memory T-cell abundance and TCR diversity-are associated with severe irAE development, independent of the affected organ system within 3 months of ICI treatment initiation. Here, we provide an extended perspective on this work, synthesize and discuss related literature, and summarize practical considerations for clinical translation. Collectively, these findings lay a foundation for data-driven and mechanistic insights into irAE development, with the potential to reduce ICI morbidity and mortality in the future.
Substances chimiques
Immune Checkpoint Inhibitors
0
Antineoplastic Agents, Immunological
0
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
96-109Subventions
Organisme : NCI NIH HHS
ID : R00 CA187192
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA237727
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA218950
Pays : United States
Informations de copyright
© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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