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.
肿瘤细胞治疗研究
英文原题:Intranasal Administration of Codium fragile Polysaccharide Elicits Anti-Cancer Immunity against Lewis Lung Carcinoma.
Intranasal Administration of Codium fragile Polysaccharide Elicits Anti-Cancer Immunity against Lewis Lung Carcinoma.
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天然多糖在调节动物免疫方面已显示出良好效果。本研究考察了经鼻给予刺松藻多糖(CFPs)对小鼠的免疫刺激作用。在C57BL/6小鼠中经鼻给予CFPs可诱导纵隔淋巴结(mLN)中巨噬细胞和树突状细胞(DCs)表面活化标志物表达上调,以及支气管肺泡灌洗液中白细胞介素-6(IL-6)、IL-12p70和肿瘤坏死因子-α的产生。
此外,经鼻给予CFP后,通过上调C-C基序趋化因子受体7的表达,mLN中常规树突状细胞(cDCs)数量增加,cDCs亚群也被激活。
另外,经鼻给予CFPs促进了mLN中自然杀伤(NK)细胞和T细胞的活化,这些细胞产生促炎细胞因子和细胞毒性介质。最后,每日给予CFPs抑制了Lewis肺癌细胞向肺部的浸润,而CFPs对肿瘤生长的预防作用需要NK细胞和CD8 T细胞。
此外,CFPs联合抗程序性细胞死亡配体1(PD-L1)抗体(Ab)改善了抗PD-L1 Ab对肺癌的治疗效果。因此,这些数据表明,经鼻给予CFP诱导了针对肺癌的黏膜免疫。
Natural polysaccharides have shown promising effects on the regulation of immunity in animals. In this study, we examined the immune stimulatory effect of intranasally administered Codium fragile polysaccharides (CFPs) in mice. Intranasal administration of CFPs in C57BL/6 mice induced the upregulation of surface activation marker expression in macrophages and dendritic cells (DCs) in the mediastinal lymph node (mLN) and the production of interleukin-6 (IL-6), IL-12p70, and tumor necrosis factor-α in bronchoalveolar lavage fluid.
Moreover, the number of conventional DCs (cDCs) was increased in the mLNs by the upregulation of C-C motif chemokine receptor 7 expression, and subsets of cDCs were also activated following the intranasal administration of CFP.
In addition, the intranasal administration of CFPs promoted the activation of natural killer (NK) and T cells in the mLNs, which produce pro-inflammatory cytokines and cytotoxic mediators.
Finally, daily administration of CFPs inhibited the infiltration of Lewis lung carcinoma cells into the lungs, and the preventive effect of CFPs on tumor growth required NK and CD8 T cells.
Furthermore, CFPs combined with anti-programmed cell death-ligand 1 (PD-L1) antibody (Ab) improved the therapeutic effect of anti-PD-L1 Ab against lung cancer.
Therefore, these data demonstrated that the intranasal administration of CFP induced mucosal immunity against lung cancer.
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