IFNβ Is a Potent Adjuvant for Cancer Vaccination Strategies

• DOI: 10.3389/fimmu.2021.735133
• Publication Date: 2021-09-06T18:02:49Z
• Authors: Katherine M. Audsley; Teagan Wagner; Clara Ta; Hannah V. Newnes; 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
• Keywords: 0301 basic medicine; Skin Neoplasms; Immunology; Melanoma, Experimental; 610; Mice, Transgenic; CD8-Positive T-Lymphocytes; CD8+ T cells; Lymphocyte Activation; Cancer Vaccines; B7-H1 Antigen; Mice; 03 medical and health sciences; Lymphocytes, Tumor-Infiltrating; adjuvant; Adjuvants, Immunologic; Cell Line, Tumor; Animals; Immune Checkpoint Inhibitors; Cell Proliferation; Vaccination; Interferon-beta; RC581-607; 3. Good health; Mice, Inbred C57BL; type I interferon; Female; cross-priming; Immunologic diseases. Allergy; cancer vaccination; IFNβ

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.