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:Processed Osteoclasts Similar to Live Osteoclasts are Capable of Supercharging Natural Killer (sNK) Cells.
Processed Osteoclasts Similar to Live Osteoclasts are Capable of Supercharging Natural Killer (sNK) Cells.
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在本文中,我们比较了经处理的破骨细胞(pOCs)与活破骨细胞(OCs)扩增/超级激活NK细胞(sNK)的能力。与活OCs相比,pOCs诱导NK细胞扩增的水平相似。与活OC生成的sNK细胞相比,pOC生成的sNK细胞对口腔鳞状癌干细胞样细胞(OSCSCs)肿瘤的裂解能力较低。与活OC生成的sNK细胞相比,pOC生成的sNK细胞中IFN-γ分泌水平也略低。即使将活OCs培养上清加入pOC-sNK培养物中,与OC-sNK培养物相比,pOC-sNK培养物的细胞毒功能和IFN-γ分泌水平仍保持较低。与活OCs相比,pOCs在sNK细胞培养物中选择CD8+ T细胞的能力相当。总体而言,尽管活OCs的激活能力略优于经处理的破骨细胞,但pOCs因NK扩增周期更短、成本效益更高以及患者输注可及性更快,更适合用于sNK细胞的扩增。
In this paper, we compared the ability to expand/supercharge NK cells (sNK) by either processed osteoclasts (pOCs) or live osteoclasts (OCs). pOCs induced similar levels of cell expansion in NK cells compared to live OCs. pOC-generated sNK cells exhibited lower lysis of oral squamous carcinoma stem-like cells (OSCSCs) tumors in comparison to live OC-generated sNK cells.
Slightly lower levels of IFN-γ secretion were also observed in pOC-generated sNK cells when compared to live OC-generated sNK cells. Cytotoxic function and secretion levels of IFN-γ remained low in pOC-sNK cultures compared to OC-sNK cultures even after adding the supernatants harvested from live OCs to pOC-sNK cultures. pOCs were equally capable of selecting CD8+ T cells in sNK cell cultures when compared to live OCs.
Overall, even though live OCs are capable of activating slightly better than the processed osteoclasts, the use of pOCs is preferable for the expansion of sNK cells due to shorter NK expansion period, higher cost-effectiveness, and faster availability for patient infusion.
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