DataSheet_1_IFNβ Is a Potent Adjuvant for Cancer Vaccination Strategies.pdf

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.

癌症疫苗可诱导抗肿瘤T细胞免疫的产生，而加入I型干扰素（type I interferons, IFNs）这类有效的免疫佐剂可增强其免疫效果。尽管已有研究证实I型干扰素可促进T细胞的交叉致敏，但各亚型的具体功能仍未明确。本研究在临床前小鼠模型中，系统比较了不同I型干扰素亚型增强全细胞疫苗策略诱导T细胞应答的能力。研究发现，与其他受试I型干扰素亚型相比，联合干扰素β（IFNβ）的疫苗可显著扩增肿瘤特异性CD8⁺ T细胞。该最优扩增效应依赖于XCR1阳性树突状细胞、CD4阳性T细胞以及CD40/CD40L信号通路的完整存在。在治疗应用中，与未添加干扰素的疫苗组相比，联合干扰素β的疫苗可延缓肿瘤进展。当联合抗PD-L1免疫检查点阻断疗法（anti-PD-L1 checkpoint blockade therapy, CPB）进行疫苗接种时，加入干扰素β可使更多小鼠实现肿瘤完全消退，且整体生存期呈现延长趋势。本研究证实了干扰素β具有强大的佐剂活性，凸显了其单独或联合免疫检查点阻断疗法增强癌症疫苗策略的应用潜力。