AUTHOR=Audsley Katherine M. , Wagner Teagan , Ta Clara , Newnes Hannah V. , Buzzai Anthony C. , Barnes Samantha A. , Wylie Ben , Armitage Jesse , Kaisho Tsuneyasu , Bosco Anthony , McDonnell Alison , Cruickshank Mark , Fear Vanessa S. , Foley Bree , Waithman Jason TITLE=IFNβ Is a Potent Adjuvant for Cancer Vaccination Strategies JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.735133 DOI=10.3389/fimmu.2021.735133 ISSN=1664-3224 ABSTRACT=

Cancer vaccination drives the generation of anti-tumor T cell immunity and can be enhanced by the inclusion of effective immune adjuvants such as type I interferons (IFNs). Whilst type I IFNs have been shown to promote cross-priming of T cells, the role of individual subtypes remains unclear. Here we systematically compared the capacity of distinct type I IFN subtypes to enhance T cell responses to a whole-cell vaccination strategy in a pre-clinical murine model. We show that vaccination in combination with IFNβ induces significantly greater expansion of tumor-specific CD8+ T cells than the other type I IFN subtypes tested. Optimal expansion was dependent on the presence of XCR1+ dendritic cells, CD4+ T cells, and CD40/CD40L signaling. Therapeutically, vaccination with IFNβ delayed tumor progression when compared to vaccination without IFN. When vaccinated in combination with anti-PD-L1 checkpoint blockade therapy (CPB), the inclusion of IFNβ associated with more mice experiencing complete regression and a trend in increased overall survival. This work demonstrates the potent adjuvant activity of IFNβ, highlighting its potential to enhance cancer vaccination strategies alone and in combination with CPB.