Frontiers in Immunology (Sep 2021)

IFNβ Is a Potent Adjuvant for Cancer Vaccination Strategies

  • Katherine M. Audsley,
  • Teagan Wagner,
  • Teagan Wagner,
  • Clara Ta,
  • Hannah V. Newnes,
  • Anthony C. Buzzai,
  • Anthony C. Buzzai,
  • Samantha A. Barnes,
  • Ben Wylie,
  • Jesse Armitage,
  • Tsuneyasu Kaisho,
  • Anthony Bosco,
  • Alison McDonnell,
  • Mark Cruickshank,
  • Vanessa S. Fear,
  • Bree Foley,
  • Jason Waithman

DOI
https://doi.org/10.3389/fimmu.2021.735133
Journal volume & issue
Vol. 12

Abstract

Read online

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.

Keywords