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Naringenin Enhances the Antitumor Effect of Therapeutic Vaccines by Promoting Antigen Cross-Presentation.

柚皮素通过促进抗原交叉呈递增强治疗性疫苗的抗肿瘤作用。

  • 影响因子:4.41
  • DOI:10.4049/jimmunol.1900278
  • 作者列表:"Wang L","Zeng W","Wang L","Wang Z","Yin X","Qin Y","Zhang F","Zhang C","Liang W
  • 发表时间:2020-02-01
Abstract

:Dendritic cells (DCs) can internalize and cross-present exogenous Ags to CD8+ T cells for pathogen or tumor cell elimination. Recently, growing evidences suggest the possible immunoregulatory role of flavonoids through modulating the Ag presentation of DCs. In this study, we report that naringenin, a grapefruit-derived flavonoid, possesses the ability to increase the Ag cross-presentation in both murine DC line DC2.4 as well as bone marrow-derived DCs, and naringenin-induced moderate intracellular oxidative stress that contributed to the disruption of lysosomal membrane enhanced Ag leakage to cytosol and cross-presentation. Moreover, in a murine colon adenocarcinoma model, naringenin induced more CD103+ DCs infiltration into tumor and facilitated the activation of CD8+ T cells and strengthened the performance of therapeutic E7 vaccine against TC-1 murine lung cancer. Our investigations may inspire novel thoughts for vaccine design and open a new field of potential applications of flavonoids as immunomodulators to improve host protection against infection and tumor.

摘要

: 树突状细胞 (DCs) 可以内化和交叉存在外源性 Ags 到 CD8 + T 细胞,用于病原体或肿瘤细胞消除。最近,越来越多的证据表明黄酮类化合物可能通过调节 DCs 的 Ag 呈递发挥免疫调节作用。在本研究中,我们报道柚皮素,一种葡萄柚来源的类黄酮,在小鼠 DC 系 DC2.4 以及骨髓来源的 DCs 中具有增加 Ag 交叉呈递的能力, 柚皮素诱导的中度细胞内氧化应激有助于溶酶体膜的破坏,增强 Ag 对胞质溶胶的渗漏和交叉呈递。此外,在小鼠结肠腺癌模型中, 柚皮素诱导更多的 CD103 + DCs 浸润到肿瘤中,促进 CD8 + T 细胞的活化,增强治疗性 E7 疫苗对 TC-1 小鼠肺癌的性能。我们的研究可能会激发疫苗设计的新思路,并开辟黄酮类化合物作为免疫调节剂的潜在应用领域,以提高宿主对感染和肿瘤的保护作用。

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影响因子:6.50
发表时间:2020-03-31
来源期刊:Cancer letters
DOI:10.1016/j.canlet.2019.12.039
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