RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The Combination of Bioavailable Concentrations of Curcumin and Resveratrol Shapes Immune Responses While Retaining the Ability to Reduce Cancer Cell Survival.
The Combination of Bioavailable Concentrations of Curcumin and Resveratrol Shapes Immune Responses While Retaining the Ability to Reduce Cancer Cell Survival.
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多酚姜黄素(CUR)和白藜芦醇(RES)因其抗肿瘤作用而被广泛报道。然而,其低生物利用度是其在治疗中应用的缺点。本研究的目的是探讨在生物可利用浓度下使用的CUR和RES是否能在保留抗肿瘤活性的同时调节免疫反应,并确定CUR和RES对外周血单核细胞(PBMCs)免疫反应的影响以及肿瘤生长抑制是否可以通过它们的联合使用得到改善。
我们证明,低剂量的CUR和RES联合使用降低了癌细胞系的存活率,但对PBMCs的活力没有影响。尽管在CUR + RES处理后,T淋巴细胞显示出增强的活化状态,但RES抵消了CUR在T细胞中诱导的IFN-表达增加,并且多酚联合使用增加了T调节细胞的IL-10产生。另一方面,联合处理通过上调和下调激活性和抑制性受体增强了NK细胞活性,并增加了单核细胞/巨噬细胞上CD68的表达水平。
总体而言,我们的结果表明,低剂量的CUR和RES联合使用差异性地塑造免疫细胞,同时保留抗肿瘤活性,支持这种多酚联合在抗癌治疗中的应用,并提示其可能作为基于NK细胞免疫疗法的佐剂应用。
The polyphenols Curcumin (CUR) and Resveratrol (RES) are widely described for their antitumoral effects.
However, their low bioavailability is a drawback for their use in therapy. The aim of this study was to explore whether CUR and RES, used at a bioavailable concentration, could modulate immune responses while retaining antitumor activity and to determine whether CUR and RES effects on the immune responses of peripheral blood mononuclear cells (PBMCs) and tumor growth inhibition could be improved by their combination.
We demonstrate that the low-dose combination of CUR and RES reduced the survival of cancer cell lines but had no effect on the viability of PBMCs. Although following CUR + RES treatment T lymphocytes showed an enhanced activated state, RES counteracted the increased IFN- expression induced by CUR in T cells and the polyphenol combination increased IL-10 production by T regulatory cells.
On the other hand, the combined treatment enhanced NK cell activity through the up- and downregulation of activating and inhibitory receptors and increased CD68 expression levels on monocytes/macrophages.
Overall, our results indicate that the combination of CUR and RES at low doses differentially shapes immune cells while retaining antitumor activity, support the use of this polyphenol combinations in anticancer therapy and suggest its possible application as adjuvant for NK cell-based immunotherapies.
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