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:Decoding the biological properties and transcriptomic landscapes of human natural killer cells derived from bone marrow and umbilical cord blood.
Decoding the biological properties and transcriptomic landscapes of human natural killer cells derived from bone marrow and umbilical cord blood.
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纵向研究强调了基于同种异体自然杀伤(NK)细胞的细胞疗法在癌症免疫监视和免疫治疗中的作用,然而,对包括脐带血(UC)和骨髓(BM)在内的候选来源NK细胞缺乏系统且详细的比较,这在很大程度上阻碍了其大规模应用。
在此,我们从单核细胞(MNC)中分离了驻留NK细胞(rUC-NK、rBM-NK),并分析了相应的扩增NK细胞对应物(eUC-NK、eBM-NK)。随后,从基因表达谱和遗传变异方面对eUC-NK和eBM-NK进行了多层面的生物信息学分析。rBM-NK组中总NK细胞或活化NK细胞的百分比分别约为rUC-NK组的2倍。相反,eUC-NK中总NK细胞的比例高于eBM-NK组,尤其是CD25+记忆样NK细胞亚群。
此外,eUC-NK和eBM-NK在基因表达模式和遗传谱方面表现出多维度的相似性和差异性,而eUC-NK和eBM-NK均表现出有效的肿瘤杀伤能力。
总之,我们剖析了来源于UC-MNC和BM-MNC的NK细胞的细胞和转录组特征,这为进一步探索所述NK细胞的特性提供了新的文献依据,并将有利于未来癌症免疫治疗的临床应用。
Longitudinal studies have highlighted allogeneic natural killer (NK) cell-based cytotherapy for cancer immunosurveillance and immunotherapy, yet the deficiency of systematic and detailed comparison of NK cells from candidate sources including umbilical cord blood (UC) and bone marrow (BM) largely hinders the large-scale application.
Herein, we isolated resident NK cells (rUC-NK, rBM-NK) from mononuclear cells (MNC), and analyzed the corresponding expanded NK cell counterparts (eUC-NK, eBM-NK). Then, the eUC-NK and eBM-NK were turned to multifaceted bioinformatics from the aspects of gene expression profiling and genetic variations.
The percentages of total or activated NK cells in rBM-NK group were approximate 2-fold higher over those in the rUC-NK group, respectively. Instead, the proportion of total NK cells in eUC-NK was higher than that in the eBM-NK group, and in particular, the CD25 + memory-like NK cell subset.
Furthermore, eUC-NK and eBM-NK manifested multidimensional similarities and diversities in gene expression pattern and genetic spectrum, whereas both eUC-NK and eBM-NK exhibited effective tumor killing capacity. Collectively, we dissected the cellular and transcriptomic signatures of NK cells generated from UC-MNC and BM-MNC, which supplied new literature for further exploring the characteristics of the indicated NK cells and would benefit the clinical application for cancer immunotherapy in future.
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