Hasmim Meriem, Khalife Nadine, Zhang Yanyan, Doldur Manale, Visentin Geralidne, Terry Stéphane, Giron-Michel Julien, Tang Ruoping, Delhommeau François, Dulphy Nicolas, Bourhis Jean-Henri, Louache Fawzia, Chouaib Salem
U1186-INSERM, Equipe labellisée Ligue contre le Cancer, Institut Gustave Roussy, 114 rue Edouard Vaillant, Villejuif, France.
INSERM U1170, Gustave Roussy, F-94805, Villejuif, France.
Oncoimmunology. 2017 Jul 18;6(10):e1346763. doi: 10.1080/2162402X.2017.1346763. eCollection 2017.
The administration of -expanded Natural Killer (NK) cells in leukemia therapy is still challenging, in part due to the difficulty to generate in sufficient quantities fully mature and functional NK cells and Identification of surface markers indicative of NK maturation and functionality is therefore needed. Here, based on the analysis of surface receptors of -expanded NK cells, we identified CD94 as a surface marker correlating with high lytic potential against leukemic cell lines and immunological synapse formation. CD94-positive -expanded NK cells displayed higher expression of NKG2 receptors and the adhesion molecule LFA-1, as compared with their CD94-negative counterparts. We also tested the anti-leukemic capacity of -expanded NK cells against patient-derived acute myeloid leukemia cells. Although no anti-leukemic effect was detected, we noticed that only CD94-positive -expanded NK cells were detected in leukemic mice at the end of the 2-week treatment. Moreover, flow cytometry analysis showed a subpopulation harboring CD94 (NK) and CD34 (leukemic cells) double staining, indicative of conjugate formation. Therefore surface expression of CD94 on -differentiated NK cells emerged as an indicator of and killer cell functionality.
在白血病治疗中,施用经扩增的自然杀伤(NK)细胞仍然具有挑战性,部分原因在于难以大量生成完全成熟且功能正常的NK细胞,因此需要鉴定指示NK细胞成熟和功能的表面标志物。在此,基于对经扩增的NK细胞表面受体的分析,我们鉴定出CD94作为一种与针对白血病细胞系的高裂解潜力以及免疫突触形成相关的表面标志物。与CD94阴性的经扩增NK细胞相比,CD94阳性的经扩增NK细胞表现出更高的NKG2受体和黏附分子LFA-1表达。我们还测试了经扩增的NK细胞对患者来源的急性髓性白血病细胞的抗白血病能力。尽管未检测到抗白血病作用,但我们注意到在为期2周的治疗结束时,在白血病小鼠中仅检测到CD94阳性的经扩增NK细胞。此外,流式细胞术分析显示存在一个同时含有CD94(NK细胞)和CD34(白血病细胞)双重染色的亚群,表明形成了共轭物。因此,在经分化的NK细胞上CD94的表面表达成为NK细胞和杀伤细胞功能的一个指标。