Activated natural killer cells predict poor clinical prognosis in high-risk B- and T-cell acute lymphoblastic leukemia.
Activated natural killer cells predict poor clinical prognosis in high-risk B- and T-cell acute lymphoblastic leukemia.
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DOI：
10.1182/blood.2020009871
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发表时间：
2021-10-21
期刊：
影响因子：
20.3
通讯作者：
Swaminathan S
中科院分区：
文献类型：
--
作者：
Duault C;Kumar A;Taghi Khani A;Lee SJ;Yang L;Huang M;Hurtz C;Manning B;Ghoda L;McDonald T;Lacayo NJ;Sakamoto KM;Carroll M;Tasian SK;Marcucci G;Yu J;Caligiuri MA;Maecker HT;Swaminathan S
Duault及其同事研究了20例B细胞或T细胞急性淋巴细胞白血病（ALL）患者的样本，发现自然杀伤（NK）效应细胞成熟缺陷，以及细胞毒性较低的过度活化的产生精氨酸的NK细胞的积累。活化的产生精氨酸的NK细胞的频率增加是ALL临床预后不良的独立预测因子。这些发现表明，NK细胞谱可能在这种情况下具有预后潜力。NK效应细胞的成熟缺陷导致B/T-ALL患者中细胞毒性较低的过度活化的产生精氨酸的NK细胞的积累。在ALL患者中，活化的产生精氨酸的NK细胞的频率增加独立地预测不良的临床结果。B和T细胞急性淋巴细胞白血病（B/T-ALL）可能是难治性的，或在治疗后通过抑制自然杀伤（NK）细胞特异性介导的宿主抗癌免疫监视而复发。我们使用质谱、流式细胞术和计算机模拟细胞术描述了高危B/T-ALL患者NK细胞的表型和功能缺陷，目的是进一步阐明NK细胞在维持急性淋巴细胞白血病（ALL）消退中的作用。我们发现，与正常细胞相比，来自B/T-ALL患者的NK细胞的细胞毒性较小，但表现出活化特征，其特征是高CD 56、高CD 69、产生活化的NK细胞来源的细胞因子和钙（Ca 2+）信号传导。我们证明了NK细胞成熟为细胞毒性效应子的缺陷会阻止ALL中的NK细胞像正常NK细胞一样有效地裂解NK细胞敏感的靶标。此外，我们发现ALL中的NK细胞被耗尽，这可能是由它们的慢性激活引起的。我们发现，活化的产生精氨酸的NK细胞的频率增加与疾病严重程度增加相关，并独立预测ALL患者的不良临床结局。我们的研究强调了开发NK细胞谱作为诊断工具预测ALL患者临床结局的益处，并强调了同种异体NK细胞输注预防ALL复发的临床潜力。
Duault and colleagues investigated samples from 20 patients with B- or T-cell acute lymphoblastic leukemia (ALL) and identified defective maturation of natural killer (NK) effector cells and accumulation of less cytotoxic hyperactivated cytokine-producing NK cells. Increased frequency of activated cytokine-producing NK cells is an independent predictor of poor clinical outcome in ALL. These findings suggest that NK cell profiling may have prognostic potential in this setting. Defective maturation of NK effector cells leads to accumulation of less cytotoxic hyperactivated cytokine-producing NK cells in patients with B/T-ALL. Increased frequency of activated cytokine-producing NK cells independently predicts poor clinical outcome in patients with ALL. B- and T-cell acute lymphoblastic leukemia (B/T-ALL) may be refractory or recur after therapy by suppressing host anticancer immune surveillance mediated specifically by natural killer (NK) cells. We delineated the phenotypic and functional defects in NK cells from high-risk patients with B/T-ALL using mass cytometry, flow cytometry, and in silico cytometry, with the goal of further elucidating the role of NK cells in sustaining acute lymphoblastic leukemia (ALL) regression. We found that, compared with their normal counterparts, NK cells from patients with B/T-ALL are less cytotoxic but exhibit an activated signature that is characterized by high CD56, high CD69, production of activated NK cell–origin cytokines, and calcium (Ca2+) signaling. We demonstrated that defective maturation of NK cells into cytotoxic effectors prevents NK cells from ALL from lysing NK cell–sensitive targets as efficiently as do normal NK cells. Additionally, we showed that NK cells in ALL are exhausted, which is likely caused by their chronic activation. We found that increased frequencies of activated cytokine-producing NK cells are associated with increased disease severity and independently predict poor clinical outcome in patients with ALL. Our studies highlight the benefits of developing NK cell profiling as a diagnostic tool to predict clinical outcome in patients with ALL and underscore the clinical potential of allogeneic NK cell infusions to prevent ALL recurrence.
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影响因子：
2.8
作者：
Geller MA;Miller JS
通讯作者：
Miller JS
影响因子：
16.8
作者：
Curran EK;Godfrey J;Kline J
通讯作者：
Kline J
DOI：
10.1126/science.1198704
发表时间：
2011-05-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bendall SC;Simonds EF;Qiu P;Amir el-AD;Krutzik PO;Finck R;Bruggner RV;Melamed R;Trejo A;Ornatsky OI;Balderas RS;Plevritis SK;Sachs K;Pe'er D;Tanner SD;Nolan GP
通讯作者：
Nolan GP
影响因子：
17.1
作者：
Brentjens RJ;Davila ML;Riviere I;Park J;Wang X;Cowell LG;Bartido S;Stefanski J;Taylor C;Olszewska M;Borquez-Ojeda O;Qu J;Wasielewska T;He Q;Bernal Y;Rijo IV;Hedvat C;Kobos R;Curran K;Steinherz P;Jurcic J;Rosenblat T;Maslak P;Frattini M;Sadelain M
通讯作者：
Sadelain M
影响因子：
20.3
作者：
Gardner, Rebecca;Wu, David;Turtle, Cameron J.
通讯作者：
Turtle, Cameron J.