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:Yeast β-glucan modulates macrophages and improves antitumor NK-cell responses in cancer.
Yeast β-glucan modulates macrophages and improves antitumor NK-cell responses in cancer.
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作为肿瘤中占比最大的髓系免疫细胞,巨噬细胞根据其不同表型在肿瘤生长和消退中发挥重要作用,因此重编程巨噬细胞已成为癌症免疫治疗的新研究方向。酵母来源的全β-葡聚糖颗粒(WGPs)可诱导M0巨噬细胞分化为M1巨噬细胞,并将M2巨噬细胞和肿瘤相关巨噬细胞(TAMs)转化为M1巨噬细胞。体外研究已证实,经WGP处理的巨噬细胞可增加NK 细胞(NK细胞)中的活化受体,并增强NK细胞的细胞毒性。细胞外调节蛋白激酶(ERK)信号通路参与WGP介导的巨噬细胞表型调控。进一步的体内研究表明,口服WGP可显著延缓肿瘤生长,这与巨噬细胞和NK细胞比例增加、巨噬细胞表型逆转以及NK细胞免疫功能增强有关。NK细胞耗竭会降低WGP在荷瘤小鼠中的治疗效果。这些发现揭示了除T细胞外,NK细胞也参与WGP的抗肿瘤过程。研究证实WGP通过调控巨噬细胞表型来调节NK细胞功能。
As the largest proportion of myeloid immune cells in tumors, macrophages play an important role in tumor growth and regression according to their different phenotypes, thus reprogramming macrophages has become a new research direction for cancer immunotherapy. Yeast-derived whole β-glucan particles (WGPs) can induce M0 macrophages to differentiate into M1 macrophages and convert M2 macrophages and tumor-associated macrophages (TAMs) into M1 macrophages.
In vitro, studies have confirmed that WGP-treated macrophages increase the activating receptors in natural killer cells (NK cells) and enhance the cytotoxicity of NK cells. The extracellular regulated protein kinases (ERK) signaling pathway is involved in WGP-mediated regulation of the macrophage phenotype.
Further in vivo studies show that oral WGP can significantly delay tumor growth, which is related to the increased proportion of macrophages and NK cells, the macrophage phenotype reversal, and the enhancement of NK cell immune function. NK-cell depletion reduces the therapeutic efficacy of WGP in tumor-bearing mice.
These findings revealed that in addition to T cells, NK cells also participate in the antitumor process of WGP. It was confirmed that WGP regulates the macrophage phenotype to regulate NK-cell function.
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