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:Natural Killer Cell Therapy Combined with Probiotic Bacteria Supplementation Restores Bone Integrity in Cancer by Promoting IFN-γ Production.
Natural Killer Cell Therapy Combined with Probiotic Bacteria Supplementation Restores Bone Integrity in Cancer by Promoting IFN-γ Production.
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本研究发现,免疫细胞分泌的干扰素-γ(IFN-γ)与胰腺荷瘤人源化-BLT(hu-BLT)小鼠骨质量变化之间存在密切关联。与健康小鼠相比,hu-BLT小鼠荷瘤导致骨吸收并降低IFN-γ产生。有趣的是,口服补充益生菌AJ2,无论是单独使用还是与超级NK(sNK)细胞联合使用,均抑制了肿瘤生长,并提高了组织隔室和肿瘤部位的IFN-γ水平。与未治疗的荷瘤小鼠相比,在接受sNK细胞和AJ2治疗的小鼠中,胰腺、脾脏、PBMCs、脾细胞来源NK细胞和骨髓的细胞培养物中观察到IFN-γ分泌增强。较高的IFN-γ水平与hu-BLT小鼠骨完整性改善相关。TRAP染色显示,未治疗的荷瘤小鼠破骨细胞活性和骨吸收增加,而接受sNK和AJ2治疗的小鼠则相反。本研究强调了免疫细胞来源IFN-γ在预防肿瘤诱导的骨丢失和改善骨质量中的作用,提示益生菌单独使用或与免疫疗法联合使用具有作为溶骨性癌症治疗手段的潜力。
This study found a strong link between interferon-gamma (IFN-γ) secretion from immune cells and changes in bone quality in pancreatic tumor-bearing humanized-BLT (hu-BLT) mice. Tumor presence in hu-BLT mice led to bone resorption and reduced IFN-γ production compared to healthy mice. Interestingly, oral supplementation with probiotic bacteria AJ2, either alone or combined with supercharged NK (sNK) cells, inhibited tumor growth and increased IFN-γ levels in tissue compartments and tumor sites.
Enhanced IFN-γ secretion was observed in cell cultures from the pancreas, spleen, PBMCs, splenocyte-derived NK cells, and bone marrow of mice treated with sNK cells and AJ2 compared to untreated tumor-bearing mice. Higher IFN-γ levels were associated with improved bone integrity in hu-BLT mice.
TRAP staining showed increased osteoclastic activity and bone resorption in untreated tumor mice, in contrast to those treated with sNK and AJ2. This research highlights the role of immune cell-derived IFN-γ in preventing tumor-induced bone loss and improving bone quality, suggesting that probiotics, alone or with immunotherapies, have potential as treatments for osteolytic cancers.
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