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:Restorative effect of Rehmanniae radix praeparata on T-cell and NK-cell-mediated immune reconstitution in mice following radiation-induced injury.
Restorative effect of Rehmanniae radix praeparata on T-cell and NK-cell-mediated immune reconstitution in mice following radiation-induced injury.
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放射后T细胞和NK细胞的功能受损会削弱抗肿瘤免疫应答。本研究旨在探讨小鼠低剂量辐射诱导损伤后T细胞和NK细胞重建的特征以及熟地黄的恢复作用。在辐射后不同时间点,评估脾脏/胸腺指数、全血细胞计数以及CD3+ T、CD4+ T、CD8+ T和NK细胞,还有CD80、CD86、MHC-I和MHC-II。
同时在有或无熟地黄处理的情况下,评估1型辅助性T(Th1)、1型细胞毒性(Tc1)、1型NK(NK1)、调节性T(Treg)和Th17细胞以及IL-12、IL-15、T-bet和foxP3。
此外,使用受辐射小鼠的B16黑色素瘤肺转移模型来证实熟地黄的恢复作用。CD3+、CD4+、CD8+ T和NK细胞在辐射后第4至6天显著下降,并在第9至11天大部分恢复。CD80、CD86和MHC-II的表达在第6天降低,并在第11天恢复。
然而,Th1、Tc1和NK1细胞产生干扰素(IFN)仍较低,而Tregs升高。熟地黄通过增加T-bet和降低foxP3表达,有效增强Th1、Tc1和NK1细胞产生IFN并抑制Tregs,从而显著减少肿瘤负荷。这些发现表明,辐射后T细胞和NK细胞介导的低效重建以Th1、Tc1和NK1细胞减少及Tregs增加为特征,熟地黄有效促进了T细胞和NK细胞亚群的功能重建,从而增强辐射后的抗肿瘤免疫。
Functional impairment of T and NK cells following irradiation (IR) undermine anti-tumor immune responses.
This study aimed to investigate the characteristics of T-cell and NK-cell reconstitution in mice following low-dose radiation-induced injury and the restorative effects of Rehmanniae Radix Praeparata (RRP).
At various time points post-IR, splenic/thymic indices, complete blood count and CD3+ T, CD4+ T, CD8+ T and NK cells, as well as CD80, CD86, MHC-I and MHC-II were assessed. Type 1 T helper (Th1), Type 1 cytotoxic (Tc1), Type 1 NK (NK1), regulatory T (Treg) and Th17 cells along with IL-12, IL-15, T-bet and foxP3 were also evaluated with or without RRP treatment.
Additionally, a B16 melanoma lung metastasis model in irradiated mice was used to confirm the restorative effects of RRP. CD3+, CD4+, CD8+ T and NK cells decreased significantly on Days 4 to 6 and largely recovered by Days 9 to 11 post-IR. The expression of CD80, CD86 and MHC-II reduced on Day 6 and recovered by Day 11.
However, interferon (IFN)- production by Th1, Tc1 and NK1 cells remained lower, whereas Tregs were elevated. RRP effectively enhanced IFN- production from Th1, Tc1 and NK1 cells and suppressed Tregs by increasing T-bet and decreasing foxP3 expression, thereby significantly reduced the tumor burden.
These findings suggest that T-Cell and NK-Cell-mediated inefficient reconstitution following IR was characterized by an decrease of Th1, Tc1 and NK1 cells and an increase of Tregs, RRP effectively promoted the functional reconstitution of T-cell and NK-cell subsets, thereby enhancing anti-tumor immunity after IR.
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