Evaluating the impact of age on immune checkpoint therapy biomarkers.
TCGA
aging
cancer
genomics
immune
immunotherapy
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
24 08 2021
24 08 2021
Historique:
received:
14
05
2021
revised:
01
07
2021
accepted:
03
08
2021
entrez:
25
8
2021
pubmed:
26
8
2021
medline:
12
2
2022
Statut:
ppublish
Résumé
Both tumors and aging alter the immune landscape of tissues. These interactions may play an important role in tumor progression among elderly patients and may suggest considerations for patient care. We leverage large-scale genomic and clinical databases to perform comprehensive comparative analysis of molecular and cellular markers of immune checkpoint blockade (ICB) response with patient age. These analyses demonstrate that aging is associated with increased tumor mutational burden, increased expression and decreased promoter methylation of immune checkpoint genes, and increased interferon gamma signaling in older patients in many cancer types studied, all of which are expected to promote ICB efficacy. Concurrently, we observe age-related alterations that might be expected to reduce ICB efficacy, such as decreases in T cell receptor diversity. Altogether, these changes suggest the capacity for robust ICB response in many older patients, which may warrant large-scale prospective study on ICB therapies among patients of advanced age.
Identifiants
pubmed: 34433020
pii: S2211-1247(21)01037-8
doi: 10.1016/j.celrep.2021.109599
pmc: PMC8757482
mid: NIHMS1735652
pii:
doi:
Substances chimiques
B7-H1 Antigen
0
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
109599Subventions
Organisme : NCI NIH HHS
ID : P30 CA006973
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG066101
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA197296
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA010815
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA247886
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests S.W. and J.X. are employees of Caris Life Sciences. E.J.F. is a consultant for Champions Oncology and is on the scientific advisory board for Viosera Therapeutics.
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