中文摘要
CD3+/CD56+自然杀伤(NK)细胞样T细胞(NKT样细胞)占血液淋巴细胞的<5%,表现出细胞毒性表型,能够杀伤多种癌症。NKT样细胞可在体外扩增为细胞因子诱导的杀伤(CIK)细胞,然而这种治疗性细胞产品在临床试验中对血液系统恶性肿瘤的结果参差不齐。
本研究的目的是确定在急性循环运动期间动员的NKT样细胞是否可用于从健康供者中生成更强效的抗肿瘤CIK细胞。一次急性运动使血液中NKT样细胞数量增加2倍。单细胞RNA测序揭示,运动动员的NKT样细胞上调了与增强抗肿瘤活性相关的基因和转录组程序,包括细胞毒性、细胞因子反应性和迁移。
然而,运动并未增强CIK细胞的体外扩增,也未在培养21天后改变其表面表型。在静息状态下、运动期间(60%和80% VO2max)或运动后(1小时)扩增的CIK细胞在体外有无细胞因子(IL-2)和抗体(OKT3)预刺激的条件下,对白血病、淋巴瘤和多发性骨髓瘤靶细胞的杀伤能力相同。
我们得出结论,健康供者中的急性运动动员了NKT样细胞,并上调了参与抗肿瘤活性的转录组程序,但并未增强CIK细胞的体外扩增。
展开英文摘要原文
CD3 + /CD56 + Natural killer (NK) cell-like T-cells (NKT-like cells) represent <5% of blood lymphocytes, display a cytotoxic phenotype, and can kill various cancers. NKT-like cells can be expanded ex vivo into cytokine-induced killer (CIK) cells, however this therapeutic cell product has had mixed results against hematological malignancies in clinical trials. The aim of this study was to determine if NKT-like cells mobilized during acute cycling exercise could be used to generate more potent anti-tumor CIK cells from healthy donors. An acute exercise bout increased NKT-like cell numbers in blood 2-fold.
Single cell RNA sequencing revealed that exercise mobilized NKT-like cells have an upregulation of genes and transcriptomic programs associated with enhanced anti-tumor activity, including cytotoxicity, cytokine responsiveness, and migration. Exercise, however, did not augment the ex vivo expansion of CIK cells or alter their surface phenotypes after 21-days of culture.
CIK cells expanded at rest, during exercise (at 60% and 80% VO 2max ) or after (1h post) were equally capable of killing leukemia, lymphoma, and multiple myeloma target cells with and without cytokine (IL-2) and antibody (OKT3) priming in vitro .
We conclude that acute exercise in healthy donors mobilizes NKT-like cells with an upregulation of transcriptomic programs involved in anti-tumor activity, but does not augment the ex vivo expansion of CIK cells.
论文信息
- 作者
- Zúñiga TM、Baker FL、Smith KA、Batatinha H、Lau B、Gustafson MP、Katsanis E、Simpson RJ
- 单位
- School of Nutritional Sciences and Wellness, The University of Arizona, Tucson, AZ, United States.United States
- 期刊
- Frontiers in immunology2022