Temporally restricted activation of IFNβ signaling underlies response to immune checkpoint therapy in mice.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 08 2022
19 08 2022
Historique:
received:
10
09
2021
accepted:
06
08
2022
entrez:
19
8
2022
pubmed:
20
8
2022
medline:
24
8
2022
Statut:
epublish
Résumé
The biological determinants of the response to immune checkpoint blockade (ICB) in cancer remain incompletely understood. Little is known about dynamic biological events that underpin therapeutic efficacy due to the inability to frequently sample tumours in patients. Here, we map the transcriptional profiles of 144 responding and non-responding tumours within two mouse models at four time points during ICB. We find that responding tumours display on/fast-off kinetics of type-I-interferon (IFN) signaling. Phenocopying of this kinetics using time-dependent sequential dosing of recombinant IFNs and neutralizing antibodies markedly improves ICB efficacy, but only when IFNβ is targeted, not IFNα. We identify Ly6C
Identifiants
pubmed: 35986006
doi: 10.1038/s41467-022-32567-8
pii: 10.1038/s41467-022-32567-8
pmc: PMC9390963
doi:
Substances chimiques
Interferon Type I
0
Interferon-alpha
0
Interferon-beta
77238-31-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4895Informations de copyright
© 2022. The Author(s).
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