Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland.
Swiss Institute of Bioinformatics (SIB), Bâtiment Génopode, Lausanne, Switzerland.
Sci Rep. 2019 Mar 14;9(1):4487. doi: 10.1038/s41598-019-40933-8.
The roles of NK cells in human melanoma remain only partially understood. We characterized NK cells from peripheral blood ex vivo by flow cytometry obtained from late stage (III/IV) melanoma patients. Interestingly, we found that the abundance of CD56 NK cells negatively correlate with overall patient survival, together with distant metastases, in a multivariate cox regression analysis. The patients' CD56 NK cells showed upregulation of CD11a, CD38 and CD95 as compared to healthy controls, pointing to an activated phenotype as well as a possible immune regulatory role in melanoma patients. After stimulation in vitro, CD56 NK cells produced less TNFα and GMCSF in patients than controls. Furthermore, IFNγ production by the CD56 NK cells correlated inversely with overall survival. Our results highlight that abundance and function of CD56 NK cells are associated with melanoma patient survival, emphasizing the potential of NK cell subsets for biomarker discovery and future therapeutic targeting.
NK 细胞在人类黑色素瘤中的作用仍不完全清楚。我们通过对晚期(III/IV 期)黑色素瘤患者的外周血进行流式细胞术分析,对 NK 细胞进行了体外鉴定。有趣的是,我们发现,在多变量 Cox 回归分析中,NK 细胞 CD56 的丰度与患者的总生存时间呈负相关,与远处转移呈负相关。与健康对照组相比,患者的 CD56 NK 细胞表达上调的 CD11a、CD38 和 CD95,表明其表型激活,并可能在黑色素瘤患者中发挥免疫调节作用。体外刺激后,患者的 CD56 NK 细胞产生的 TNFα 和 GMCSF 比对照组少。此外,CD56 NK 细胞 IFNγ 的产生与总生存期呈负相关。我们的研究结果表明,CD56 NK 细胞的丰度和功能与黑色素瘤患者的生存有关,这强调了 NK 细胞亚群在生物标志物发现和未来治疗靶点方面的潜力。