IFNβ Is a Potent Adjuvant for Cancer Vaccination Strategies

被引:15
作者
Audsley, Katherine M. [1 ]
Wagner, Teagan [1 ,2 ]
Ta, Clara [1 ]
Newnes, Hannah, V [1 ]
Buzzai, Anthony C. [1 ,3 ]
Barnes, Samantha A. [1 ]
Wylie, Ben [1 ]
Armitage, Jesse [1 ]
Kaisho, Tsuneyasu [4 ]
Bosco, Anthony [1 ]
McDonnell, Alison [1 ]
Cruickshank, Mark [5 ]
Fear, Vanessa S. [1 ]
Foley, Bree [1 ]
Waithman, Jason [1 ]
机构
[1] Univ Western Australia, Telethon Kids Inst, Nedlands, WA, Australia
[2] Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Melbourne, Vic, Australia
[3] Univ Magdeburg, Dept Expt Dermatol, Magdeburg, Germany
[4] Wakayama Med Univ, Inst Adv Med, Dept Immunol, Wakayama, Japan
[5] Univ Western Australia, Sch Biomed Sci, Nedlands, WA, Australia
关键词
type I interferon; IFN beta; cancer vaccination; adjuvant; cross-priming; CD8+T cells; checkpoint blockade; immunotherapy; CD8(+) T-CELLS; CD8-ALPHA(+) DENDRITIC CELLS; NATURAL-KILLER-CELLS; I INTERFERONS; BIOLOGICAL-ACTIVITIES; RECEPTOR; VACCINES; ALPHA; RESPONSES; MELANOMA;
D O I
10.3389/fimmu.2021.735133
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
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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页数:11
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