Hesperetin (HES) is a dihydroflavone with the molecular formula of C16H14O6. It has been reported that Hesperetin has antioxidant and anticancer effects. Recent studies showed that it can also regulate immune responses. To assess its potential function as a vaccine adjuvant, we formulated HES with inactivated B16F10 melanoma cells and determined whether it would enhance the activation of antigen-presenting cells by experiments in vivo and in vitro. We found that HES activated the PI3K-Akt signalling pathway in antigen-presenting cells (APCs), enhanced cytotoxic T lymphocyte (CTL) responses and deactivated tolerogenic T cells. We also observed that inactivated B16F10 cells in combination with HES vaccine inhibited the growth of mice tumours, resulting in improved overall survival compared to the effects of inactivated B16F10 cell vaccine. To verify that CD8+ T cells play a key role in inhibiting the development of melanoma, we transferred the sorted CD8+ T cells from immunized mice to B16F10 challenged models and found that the survival rate of tumour-bearing mice was significantly prolonged. Taken together, these results suggest that hesperetin can be used as a potential adjuvant to improve tumour immune responses and antigen immunogenicity.

中文翻译：

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橙皮素作为佐剂通过刺激细胞毒性CD8 + T细胞增强B16F10黑色素瘤的保护性抗肿瘤免疫应答。

橙皮素（HES）是分子式为C16H14O6的二氢黄酮。据报道，橙皮素具有抗氧化和抗癌作用。最近的研究表明，它也可以调节免疫反应。为了评估其作为疫苗佐剂的潜在功能，我们通过体内和体外实验将HES配制成灭活的B16F10黑色素瘤细胞，并确定它是否会增强抗原呈递细胞的激活。我们发现，HES激活了抗原呈递细胞（APC）中的PI3K-Akt信号传导途径，增强了细胞毒性T淋巴细胞（CTL）的反应，并使致耐受性T细胞失活。我们还观察到，与灭活的B16F10细胞疫苗相比，灭活的B16F10细胞与HES疫苗结合可抑制小鼠肿瘤的生长，从而提高总体存活率。为了验证CD8 + T细胞在抑制黑素瘤的发展中起关键作用，我们将分类后的CD8 + T细胞从免疫小鼠转移到B16F10攻击的模型中，发现荷瘤小鼠的存活率显着延长。综上所述，这些结果表明橙皮素可用作改善肿瘤免疫应答和抗原免疫原性的潜在佐剂。