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:Selective Expansion of NKG2C+ Adaptive NK Cells Using K562 Cells Expressing HLA-E.
Selective Expansion of NKG2C+ Adaptive NK Cells Using K562 Cells Expressing HLA-E.
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表达自身特异性抑制性杀伤细胞免疫球蛋白样受体(KIR)的适应性自然杀伤(NK)细胞可在体内响应人巨细胞病毒(HCMV)感染而扩增。开发一种优先扩增该亚群的方法对于有效靶向同种异体癌细胞至关重要。此前一项研究开发了一种体外方法,用于生成单一KIR+ NK细胞以增强对原发性急性淋巴细胞白血病细胞的靶向;然而,扩增率相当低。在此,我们提出了一种使用基因修饰的K562-HLA-E饲养细胞的有效扩增方法,用于适应性NK细胞的长期增殖,这些细胞表现出高度分化的表型以及相当的细胞毒性、CD107a和干扰素-γ(IFN-γ)产生能力。更重要的是,我们的扩增方法在培养6周后实现了适应性NK细胞超过10,000倍的扩增,为针对癌症的细胞治疗提供了高产量的同种异体反应性NK细胞。
Adaptive natural killer (NK) cells expressing self-specific inhibitory killer-cell immunoglobulin-like receptors (KIRs) can be expanded in vivo in response to human cytomegalovirus (HCMV) infection. Developing a method to preferentially expand this subset is essential for effective targeting of allogeneic cancer cells. A previous study developed an in vitro method to generate single KIR+ NK cells for enhanced targeting of the primary acute lymphoblastic leukemia cells; however, the expansion rate was quite low.
Here, we present an effective expansion method using genetically modified K562-HLA-E feeder cells for long-term proliferation of adaptive NK cells displaying highly differentiated phenotype and comparable cytotoxicity, CD107a, and interferon-γ (IFN-γ) production. More importantly, our expansion method achieved more than a 10,000-fold expansion of adaptive NK cells after 6 weeks of culture, providing a high yield of alloreactive NK cells for cell therapy against cancer.
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