Rey Jérôme, Fauriat Cyril, Kochbati Eloïse, Orlanducci Florence, Charbonnier Aude, D'Incan Evelyne, Andre Pascale, Romagne François, Barbarat Bernadette, Vey Norbert, Olive Daniel
Département d'Hématologie, Institut Paoli-Calmettes, Marseille, France; Plateforme d'Immunomonitoring en Cancérologie de Marseille, Institut Paoli-Calmettes, Marseille, France.
Plateforme d'Immunomonitoring en Cancérologie de Marseille, Institut Paoli-Calmettes, Marseille, France; Centre de Recherche en Cancérologie de Marseille, INSERM U1068, Institut Paoli-Calmettes, Aix-Marseille Université, UM105, CNRS, UMR7258, Marseille, France.
Front Immunol. 2017 Feb 2;8:64. doi: 10.3389/fimmu.2017.00064. eCollection 2017.
NK cells are defective in acute myeloid leukemia (AML) at diagnosis. Here, we studied the kinetic of expression of the major activating and inhibitory receptors of NK, CD8 T, and γδ T cells in patients undergoing chemotherapy (CT) for the treatment of AML ( = 29). We showed that NK cells are the main affected population at diagnosis and that expression of activating receptors is partially restored within a few weeks after CT. CD8 T cells and γδ T cells are only weakly affected at diagnosis. Killer cell immunoglobulin-like receptor expression by NK cells, but not NKG2A and CD85j, was downregulated. Interestingly, the development of NK cells appeared altered as the most immature CD56 NK cells were seriously underrepresented. Finally, we showed that NK cell functions were only partially restored 6 weeks after CT as degranulation capabilities of NK cells recovered, whereas cytokine production remained low. Our data point out NK cells as antitumor effectors peculiarly hampered by leukemic cells. This study may indicate a timeline when NK-mediated therapies or other immunotherapies could be performed, particularly for patients excluded of hematopoietic stem cell transplantation.
自然杀伤(NK)细胞在急性髓系白血病(AML)诊断时存在缺陷。在此,我们研究了29例接受化疗(CT)治疗AML患者中NK细胞、CD8 T细胞和γδ T细胞主要激活和抑制受体的表达动力学。我们发现,NK细胞是诊断时主要受影响的细胞群体,且激活受体的表达在CT治疗后的几周内部分恢复。CD8 T细胞和γδ T细胞在诊断时仅受到轻微影响。NK细胞的杀伤细胞免疫球蛋白样受体表达下调,但NKG2A和CD85j未下调。有趣的是,NK细胞的发育似乎发生了改变,因为最不成熟的CD56 NK细胞严重减少。最后,我们表明,CT治疗6周后NK细胞功能仅部分恢复,NK细胞的脱颗粒能力恢复,而细胞因子产生仍然较低。我们的数据指出NK细胞是特别受到白血病细胞阻碍的抗肿瘤效应细胞。这项研究可能表明了进行NK细胞介导的治疗或其他免疫治疗的时间线,特别是对于那些被排除在造血干细胞移植之外的患者。