槲皮素通过黑色素瘤中的 PDK1/CD47 轴限制肿瘤免疫逃逸

The American journal of Chinese medicine Pub Date : 2024-01-01 Epub Date: 2024-03-16 DOI:10.1142/S0192415X2450023X
Xin Li, Xue He, Bing Lin, Li Li, Qifeng Deng, Chengzhi Wang, Jing Zhang, Ying Chen, Jingyi Zhao, Xinrui Li, Yan Li, Qing Xi, Rongxin Zhang
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引用次数: 0

摘要

槲皮素(3,3[分子式:见正文],4[分子式:见正文],5,7-五羟基黄酮)是一种具有生物活性的植物黄酮类化合物,在水果和蔬菜中含量丰富,能有效抑制多种肿瘤的生长,且无毒性。然而,槲皮素对黑色素瘤免疫学的影响尚未确定。本研究旨在通过体内和体外方法研究槲皮素对黑色素瘤抗肿瘤免疫作用的作用和机制。我们的研究发现,槲皮素能够通过提高M1巨噬细胞、CD8[式:见正文] T淋巴细胞和CD4[式:见正文] T淋巴细胞的比例,促进CD8[式:见正文] T细胞分泌IL-2和IFN-[式:见正文],从而调节肿瘤免疫微环境,增强抗肿瘤免疫力,进而抑制黑色素瘤的生长。此外,我们还发现槲皮素能以剂量依赖的方式抑制 B16 细胞的增殖和迁移。此外,下调 PDK1 可抑制 CD47 的 mRNA 和蛋白表达水平。在拯救实验中,我们过量表达了 PDK1,发现 CD47 的蛋白和 mRNA 表达水平相应升高,而加入槲皮素则逆转了这一效应。此外,槲皮素还能刺激CD8[公式:见正文] T细胞的增殖并增强其功能。因此,我们的研究结果发现了槲皮素调控CD47促进吞噬的新机制,并阐明了槲皮素对肿瘤免疫微环境中巨噬细胞和CD8[式:见正文] T细胞的调控作用。将槲皮素作为一种治疗药物可为免疫疗法带来潜在的益处,提高现有黑色素瘤疗法的疗效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Quercetin Limits Tumor Immune Escape through PDK1/CD47 Axis in Melanoma.

Quercetin (3,3[Formula: see text],4[Formula: see text],5,7-pentahydroxyflavone) is a bioactive plant-derived flavonoid, abundant in fruits and vegetables, that can effectively inhibit the growth of many types of tumors without toxicity. Nevertheless, the effect of quercetin on melanoma immunology has yet to be determined. This study aimed to investigate the role and mechanism of the antitumor immunity action of quercetin in melanoma through both in vivo and in vitro methods. Our research revealed that quercetin has the ability to boost antitumor immunity by modulating the tumor immune microenvironment through increasing the percentages of M1 macrophages, CD8[Formula: see text] T lymphocytes, and CD4[Formula: see text] T lymphocytes and promoting the secretion of IL-2 and IFN-[Formula: see text] from CD8[Formula: see text] T cells, consequently suppressing the growth of melanoma. Furthermore, we revealed that quercetin can inhibit cell proliferation and migration of B16 cells in a dose-dependent manner. In addition, down-regulating PDK1 can inhibit the mRNA and protein expression levels of CD47. In the rescue experiment, we overexpressed PDK1 and found that the protein and mRNA expression levels of CD47 increased correspondingly, while the addition of quercetin reversed this effect. Moreover, quercetin could stimulate the proliferation and enhance the function of CD8[Formula: see text] T cells. Therefore, our results identified a novel mechanism through which CD47 is regulated by quercetin to promote phagocytosis, and elucidated the regulation of quercetin on macrophages and CD8[Formula: see text] T cells in the tumor immune microenvironment. The use of quercetin as a therapeutic drug holds potential benefits for immunotherapy, enhancing the efficacy of existing treatments for melanoma.

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