High-dimensional mass cytometry analysis of NK cell alterations in AML identifies a subgroup with adverse clinical outcome.
High-dimensional mass cytometry analysis of NK cell alterations in AML identifies a subgroup with adverse clinical outcome.
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AML中NK细胞改变的高维质量细胞仪分析鉴定了具有不良临床结果的亚组。
DOI：
10.1073/pnas.2020459118
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发表时间：
2021-06-01
影响因子：
11.1
通讯作者：
Olive D
中科院分区：
文献类型：
--
作者：
Chretien AS;Devillier R;Granjeaud S;Cordier C;Demerle C;Salem N;Wlosik J;Orlanducci F;Gorvel L;Fattori S;Hospital MA;Pakradouni J;Gregori E;Paul M;Rochigneux P;Pagliardini T;Morey M;Fauriat C;Dulphy N;Toubert A;Luche H;Malissen M;Blaise D;Nunès JA;Vey N;Olive D
本研究报告了非病毒诱导的恶性肿瘤中非常规CD56、−、CD16+NK细胞的蓄积。CD56CD16+NK细胞频率的增加与急性髓系白血病的不良临床结局以及其他成熟缺陷有关，并可能导致对急性髓细胞白血病进展的缺陷控制。假时间分析强调了AML患者常规NK细胞成熟过程的中断，导致健康受试者中没有分叉点。这一分析结合在急性髓细胞白血病患者中观察到的常规NK细胞频率的降低，表明非常规CD56CD16+NK细胞来自于常规NK细胞的异常成熟。总之，CD56、−、CD16+NK细胞的聚集可能是免疫逃避天然免疫的一个重要特征。自然杀伤(NK)细胞是主要的抗白血病免疫效应器。白血病细胞对NK细胞的功能有负面影响，并促进表型和功能受损的NK细胞的出现。在目前的工作中，我们强调了CD56HIV-1+非常规NK细胞在急性髓系白血病中的积累，这是一个异常的亚群，最初被描述为在慢性感染−-1的患者中升高。对48例初诊AML患者(HEMATOBIO队列，NCT02320656)和18例健康体检者(n=18)外周血进行NK细胞深度表型分析。我们发现27%的患者CD56、−、CD16+非常规NK细胞有中度到重度积聚。这些NK细胞显示NKG2A以及触发受体NKp30和NKp46的表达减少，这与先前在HIV感染患者中观察到的情况一致。这些NK细胞的高维度特征突出表明，NK细胞激活所需的另外三个主要触发受体NKG2D、dNaM-1和CD96的表达减少。初诊时CD56CD16+NK细胞比例高与不良临床结局、总生存期(HR=0.13；P=0.0002)和无事件生存期(HR=0.33；P=0.018)相关，多因素分析仍具有统计学意义。对NK细胞的假时间分析表明，成熟过程被破坏，从传统的NK细胞向CD56CD16+的−细胞分化。总之，我们的数据提示CD56AML CD16+NK细胞的积聚可能是−进展过程中免疫逃避先天免疫的结果。
This work provides a report of accumulation of unconventional CD56−CD16+ NK cells in nonvirally induced malignancies. Increased frequency of CD56−CD16+ NK cells is associated with adverse clinical outcome in AML, as well as other maturation defects, and might contribute to a defective control of AML progression. Pseudotime analysis highlights a disruption in the maturation process of conventional NK cells in AML patients, leading to a bifurcation point absent in healthy subjects. This analysis, combined with the reduced frequency of conventional NK cells observed in AML patients, suggests that unconventional CD56−CD16+ NK cells derive from an aberrant maturation of conventional NK cells. Overall, accumulation of CD56−CD16+ NK cells could be an important feature of immune escape from innate immunity. Natural killer (NK) cells are major antileukemic immune effectors. Leukemic blasts have a negative impact on NK cell function and promote the emergence of phenotypically and functionally impaired NK cells. In the current work, we highlight an accumulation of CD56−CD16+ unconventional NK cells in acute myeloid leukemia (AML), an aberrant subset initially described as being elevated in patients chronically infected with HIV-1. Deep phenotyping of NK cells was performed using peripheral blood from patients with newly diagnosed AML (n = 48, HEMATOBIO cohort, NCT02320656) and healthy subjects (n = 18) by mass cytometry. We showed evidence of a moderate to drastic accumulation of CD56−CD16+ unconventional NK cells in 27% of patients. These NK cells displayed decreased expression of NKG2A as well as the triggering receptors NKp30 and NKp46, in line with previous observations in HIV-infected patients. High-dimensional characterization of these NK cells highlighted a decreased expression of three additional major triggering receptors required for NK cell activation, NKG2D, DNAM-1, and CD96. A high proportion of CD56−CD16+ NK cells at diagnosis was associated with an adverse clinical outcome and decreased overall survival (HR = 0.13; P = 0.0002) and event-free survival (HR = 0.33; P = 0.018) and retained statistical significance in multivariate analysis. Pseudotime analysis of the NK cell compartment highlighted a disruption of the maturation process, with a bifurcation from conventional NK cells toward CD56−CD16+ NK cells. Overall, our data suggest that the accumulation of CD56−CD16+ NK cells may be the consequence of immune escape from innate immunity during AML progression.
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影响因子：
6
作者：
Lima, M;Almeida, J;Orfao, A
通讯作者：
Orfao, A
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32.4
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Mavilio, Domenico
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Hong, Henoch S.;Eberhard, Johanna M.;Meyer-Olson, Dirk
通讯作者：
Meyer-Olson, Dirk
影响因子：
4.4
作者：
Khaznadar, Zena;Boissel, Nicolas;Toubert, Antoine
通讯作者：
Toubert, Antoine