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解析源自骨髓和脐带血的人类自然杀伤细胞的生物学特性和转录组图谱。

Decoding the biological properties and transcriptomic landscapes of human natural killer cells derived from bone marrow and umbilical cord blood.

作者信息

Xie Baoguo, Zhang Leisheng, Gao Jianhua, Wang Ti'er, Liu Min, Feng Xiaoming, Xu Xianghong, Ma Shixun, Cai Hui, Guo Tiankang, Huang Weibin, Tu Xiaoyan, Wang Shuling, Yang Hongju, Fang Yihu, Li Feifei, Chen Cunrong

机构信息

Reproductive Medicine Center, The First Affiliated Hospital of Hainan Medical University, Key Laboratory of Reproductive Health Diseases Research and Translation (Hainan Medical University), Ministry of Education Haikou 570102, Hainan, China.

Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province & NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital Lanzhou 730000, Gansu, China.

出版信息

Am J Cancer Res. 2023 May 15;13(5):2087-2103. eCollection 2023.

Abstract

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.

摘要

纵向研究突出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,包括脐带血(UC)和骨髓(BM)在内的候选来源的NK细胞缺乏系统和详细的比较,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)中分离出驻留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)。然后,从基因表达谱和基因变异方面对eUC-NK和eBM-NK进行了多方面的生物信息学分析。rBM-NK组中总NK细胞或活化NK细胞的百分比分别比rUC-NK组高约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在基因表达模式和基因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。总体而言,我们剖析了从UC-MNC和BM-MNC产生的NK细胞的细胞和转录组特征,为进一步探索上述NK细胞的特性提供了新文献,并将有利于未来癌症免疫治疗的临床应用。

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