Temporally restricted activation of IFNβ signaling underlies response to immune checkpoint therapy in mice.

ABSTRACT: 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⁺/CD11b⁺ inflammatory monocytes as the primary source of IFNβ

SUBMITTER: Zemek RM 

PROVIDER: S-EPMC9390963 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature