NK92 cells and peripheral blood NK cells respond oppositely upon dasatinib treatment

IF 4.9 3区 医学 Q2 IMMUNOLOGY Immunology Pub Date : 2024-02-15 DOI:10.1111/imm.13768
Fengqi Li, Zhongyi Wang, Dongpeng Zheng, Zhaojun Pang, Chunjing Feng, Yue Ma, Ce Yang, Xueren Li, Shouchun Peng, Zichuan Liu, Xin Mu
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Abstract

Natural killer (NK) cell is a valuable tool for immunotherapy in cancer treatment, both the cultured cell line NK92 and primary NK cells are widely studied and used in research and clinical trials. Clinical observations witnessed the improvement of patients' NK cells in terms of cell counts and cytotoxic activity upon dasatinib treatment, an approved drug for chronic myeloid leukaemia and Ph+ acute lymphocytic leukaemia. Several studies supported the clinical observations, yet others argued a detrimental effect of dasatinib on NK cells. Due to the complex conditions in different studies, the definite influence of dasatinib on NK92 and primary NK cells remains to be settled. Here, we used a well-defined in vitro system to evaluate the effects of dasatinib on NK92 cells and peripheral blood (PB)-NK cells. By co-culturing NK cells with dasatinib to test the cell counts and target cell-killing activities, we surprisingly found that the chemical influenced oppositely on these two types of NK cells. While dasatinib suppressed NK92 cell proliferation and cytotoxic activity, it improved PB-NK-killing tumour cells. RNA sequencing analysis further supported this finding, uncovering several proliferating and cytotoxic pathways responding invertedly between them. Our results highlighted an intrinsic difference between NK92 and PB-NK cells and may build clues to understand how dasatinib interacts with NK cells in vivo.

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NK92 细胞和外周血 NK 细胞对达沙替尼治疗的反应截然相反。
自然杀伤(NK)细胞是治疗癌症的重要免疫疗法工具,培养细胞系 NK92 和原代 NK 细胞在研究和临床试验中都得到了广泛的研究和应用。达沙替尼是一种获准用于治疗慢性髓性白血病和 Ph+ 急性淋巴细胞白血病的药物,临床观察表明,达沙替尼治疗后,患者的 NK 细胞在细胞数量和细胞毒性活性方面都有所改善。有几项研究支持临床观察结果,但也有一些研究认为达沙替尼对NK细胞有不利影响。由于不同研究的条件复杂,达沙替尼对NK92和原代NK细胞的明确影响仍有待确定。在这里,我们使用了一个定义明确的体外系统来评估达沙替尼对NK92细胞和外周血(PB)-NK细胞的影响。通过将NK细胞与达沙替尼共同培养来检测细胞数量和靶细胞杀伤活性,我们惊讶地发现,这种化学物质对这两种类型的NK细胞产生了相反的影响。达沙替尼抑制了NK92细胞的增殖和细胞毒性活性,却提高了PB-NK杀伤肿瘤细胞的能力。RNA测序分析进一步证实了这一发现,发现了几种增殖和细胞毒性途径,它们之间的反应是相反的。我们的研究结果突显了NK92细胞和PB-NK细胞之间的内在差异,并可能为了解达沙替尼如何在体内与NK细胞相互作用提供线索。
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来源期刊
Immunology
Immunology 医学-免疫学
CiteScore
11.90
自引率
1.60%
发文量
175
审稿时长
4-8 weeks
期刊介绍: Immunology is one of the longest-established immunology journals and is recognised as one of the leading journals in its field. We have global representation in authors, editors and reviewers. Immunology publishes papers describing original findings in all areas of cellular and molecular immunology. High-quality original articles describing mechanistic insights into fundamental aspects of the immune system are welcome. Topics of interest to the journal include: immune cell development, cancer immunology, systems immunology/omics and informatics, inflammation, immunometabolism, immunology of infection, microbiota and immunity, mucosal immunology, and neuroimmunology. The journal also publishes commissioned review articles on subjects of topical interest to immunologists, and commissions in-depth review series: themed sets of review articles which take a 360° view of select topics at the heart of immunological research.
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