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:An Extended Flow Cytometry Evaluation of ex Vivo Expanded NK Cells Using K562.Clone1, a Feeder Cell Line Manufactured in Brazil.
An Extended Flow Cytometry Evaluation of ex Vivo Expanded NK Cells Using K562.Clone1, a Feeder Cell Line Manufactured in Brazil.
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NK细胞在抗癌免疫中发挥关键作用,但有效治疗所需的细胞数量难以获得,因此需要体外扩增策略。本研究构建表达膜结合IL-21和4-1BB配体的K562.Clone1饲养细胞系,以促进NK细胞扩增并维持杀伤能力。外周血NK细胞与该饲养细胞共培养14天后约扩增94倍,扩增细胞仍能杀伤急性髓系白血病原始细胞及白血病和胶质瘤细胞系。CD56、CD16、抑制性KIR和活化受体保持表达且比例平衡。研究成功开发可有效体外扩增NK细胞并保留细胞毒性的饲养细胞系,可能推动NK细胞疗法发展,尤其有助于巴西相关研究。
Natural killer (NK) cells play a crucial role in the immune system's response against cancer.
However, the challenge of obtaining the required quantity of NK cells for effective therapeutic response necessitates the development of strategies for their ex vivo expansion.
This study aimed to develop a novel feeder cell line, K562. Clone1, capable of promoting the ex vivo expansion of NK cells while preserving their cytotoxic potential. he K562 leukemic cell line was transduced with mbIL-21 and 4-1BBL proteins to generate K562. Clone1 cells. NK cells were then co-cultured with these feeder cells, and their expansion rate was monitored over 14 days.
The cytotoxic potential of the expanded NK cells was evaluated against acute myeloid leukemia blasts and tumor cell lines of leukemia and glial origin. Statistical analysis was performed to determine the significance of the results. The K562. Clone1 co-cultured with peripheral NK showed a significant increase in cell count, with an approximate 94-fold expansion over 14 days. Expanded NK cells demonstrated cytotoxicity against the tested tumor cell lines, indicating preservation of their cytotoxic characteristics.
Additionally, the CD56, CD16, inhibitory KIRs, and activation receptors were conserved and present in a well-balanced manner. The study successfully developed a feeder cell line, K562. Clone1, that effectively promotes the expansion of NK cells ex vivo while maintaining their cytotoxic potential. This development could significantly contribute to the advancement of NK cell therapy, especially in Brazil.
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