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:Supercharged Natural Killer (sNK) Cells Inhibit Melanoma Tumor Progression and Restore Endogenous NK Cell Function in Humanized BLT Mice.
Supercharged Natural Killer (sNK) Cells Inhibit Melanoma Tumor Progression and Restore Endogenous NK Cell Function in Humanized BLT Mice.
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该治疗策略不仅逆转了肿瘤进展,还恢复了内源性 NK 细胞的功能,有可能逆转肿瘤细胞在癌症患者中诱导的免疫抑制效应。
我们此前已在人源化 BLT(hu-BLT)小鼠中显示,单次输注超级活化 NK(sNK)细胞可显著预防并清除移植的口腔癌、胰腺癌和子宫癌。
本研究将相关工作扩展至黑色素瘤,考察 sNK 细胞治疗是否存在不同应答。
在 hu-BLT 小鼠中研究 sNK 细胞的安全性和组织分布,并评估其对小鼠外周血来源 PBMC、骨髓和脾脏的影响。
sNK 细胞输注有效抑制 hu-BLT 小鼠黑色素瘤生长。细胞可经外周血到达脾脏和骨髓,并浸润肿瘤部位,诱导体内黑色素瘤分化。此外,输注 sNK 细胞提高 hu-BLT 小鼠外周血 NK 细胞比例,并恢复黑色素瘤荷瘤小鼠外周血、脾脏和骨髓中的细胞毒性及 IFN-γ 分泌。
这一治疗方法不仅逆转肿瘤进展,还恢复内源性 NK 细胞功能,可能逆转癌细胞在患者体内诱导的免疫抑制效应。
We have previously shown the remarkable impact of a single infusion of supercharged NK cells (sNK) in preventing and eliminating oral, pancreatic, and uterine cancers implanted in humanized BLT (hu-BLT) mice.
In this report, we extended the studies to melanoma tumors to observe whether there were differences in response to sNK cells.
We investigated the safety and tissue biodistribution profile of sNK cells in hu-BLT mice. This included the effect of sNK cell therapy on the peripheral blood-derived PBMCs, bone marrow, and spleen of hu-BLT mice.
Our investigation showed promising outcomes, as sNK cell infusions effectively inhibited melanoma tumor growth in hu-BLT mice. These potent cells not only traversed through the peripheral blood, spleen, and bone marrow but also infiltrated the tumor site, triggering in vivo differentiation of melanoma tumors. Moreover, the infusion of sNK cells increased the percentages of NK cells in the peripheral blood of hu-BLT mice, restoring cytotoxicity and IFN- secretion within the peripheral blood, spleen, and bone marrow of melanoma-bearing mice.
This therapeutic approach not only reversed tumor progression but also revitalized the functionality of endogenous NK cells, potentially reversing the immunosuppressive effects induced by tumor cells in cancer patients.
在 PubMed 查看 → 出版商原文(DOI) 全文 PDF(PMC)· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →
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