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

• DOI: 10.1038/s41467-022-32567-8
• Publication Date: 2022-08-19T19:02:41Z
• Authors: Rachael M. Zemek; Wee Loong Chin; Vanessa S. Fear; Ben Wylie; Thomas H. Casey; Cath Forbes; Caitlin M. Tilsed; Louis Boon; Belinda B. Guo; Anthony Bosco; Alistair R. R. Fo...; Michael J. Millward; Anna K. Nowak; Richard A. Lake; Timo Lassmann; W. Joost Lesterhuis
• Keywords: Immune checkpoint

Abstract The biological determinants of the response to immune checkpoint blockade (ICB) in cancer remain incompletely understood. Little is known about dynamic events that underpin therapeutic efficacy due inability frequently sample tumours patients. Here, we map transcriptional profiles 144 responding and non-responding within two mouse models at four time points during ICB. We find display on/fast-off kinetics type-I-interferon (IFN) signaling. Phenocopying this using time-dependent sequential dosing recombinant IFNs neutralizing antibodies markedly improves ICB efficacy, but only when IFNβ targeted, not IFNα. identify Ly6C + /CD11b inflammatory monocytes as primary source active type-I-IFN signaling tumour-infiltrating associated with T cell expansion patients treated Together, our results suggest modulation critical ICB, which can be exploited drive clinical outcomes towards response.