Ifn Beta Is A Potent Adjuvant For Cancer Vaccination Strategies

FRONTIERS IN IMMUNOLOGY(2021)

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摘要
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 IFN beta 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 IFN beta delayed tumor progression when compared to vaccination without IFN. When vaccinated in combination with anti-PD-L1 checkpoint blockade therapy (CPB), the inclusion of IFN beta associated with more mice experiencing complete regression and a trend in increased overall survival. This work demonstrates the potent adjuvant activity of IFN beta, highlighting its potential to enhance cancer vaccination strategies alone and in combination with CPB.

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关键词
type I interferon, IFN beta, cancer vaccination, adjuvant, cross-priming, CD8+T cells, checkpoint blockade, immunotherapy
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