Membrane-localized neoantigens predict the efficacy of cancer immunotherapy.
biomarkers
cancer
cell membrane
immunotherapy
neoantigens
tumor mutational burden
Journal
Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894
Informations de publication
Date de publication:
15 08 2023
15 08 2023
Historique:
received:
09
04
2022
revised:
24
12
2022
accepted:
13
07
2023
medline:
18
8
2023
pubmed:
9
8
2023
entrez:
8
8
2023
Statut:
ppublish
Résumé
Immune checkpoint immunotherapy (ICI) can re-activate immune reactions against neoantigens, leading to remarkable remission in cancer patients. Nevertheless, only a minority of patients are responsive to ICI, and approaches for prediction of responsiveness are needed to improve the success of cancer treatments. While the tumor mutational burden (TMB) correlates positively with responsiveness and survival of patients undergoing ICI, the influence of the subcellular localizations of the neoantigens remains unclear. Here, we demonstrate in both a mouse melanoma model and human clinical datasets of 1,722 ICI-treated patients that a high proportion of membrane-localized neoantigens, particularly at the plasma membrane, correlate with responsiveness to ICI therapy and improved overall survival across multiple cancer types. We further show that combining membrane localization and TMB analyses can enhance the predictability of cancer patient response to ICI. Our results may have important implications for establishing future clinical guidelines to direct the choice of treatment toward ICI.
Identifiants
pubmed: 37552990
pii: S2666-3791(23)00298-7
doi: 10.1016/j.xcrm.2023.101145
pmc: PMC10439248
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
101145Subventions
Organisme : NCI NIH HHS
ID : R01 CA219304
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM150375
Pays : United States
Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The University of Chicago has filed for patent protection for biomarkers described in this work, of which P.S.B., Z.G., S.H., and J.A.H. are inventors.
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