Multidimensional Analyses of Donor Memory-Like NK Cells Reveal New Associations with Response after Adoptive Immunotherapy for Leukemia.
Multidimensional Analyses of Donor Memory-Like NK Cells Reveal New Associations with Response after Adoptive Immunotherapy for Leukemia.
复制标题
对供体记忆样的NK细胞的多维分析揭示了白血病的继发性免疫疗法后与反应的新关联。
DOI：
10.1158/2159-8290.cd-20-0312
复制
发表时间：
2020-12
期刊：
影响因子：
28.2
通讯作者：
Fehniger TA
中科院分区：
文献类型：
--
作者：
Berrien-Elliott MM;Cashen AF;Cubitt CC;Neal CC;Wong P;Wagner JA;Foster M;Schappe T;Desai S;McClain E;Becker-Hapak M;Foltz JA;Cooper ML;Jaeger N;Srivatsan SN;Gao F;Romee R;Abboud CN;Uy GL;Westervelt P;Jacoby MA;Pusic I;Stockerl-Goldstein KE;Schroeder MA;DiPersio J;Fehniger TA
NK细胞是一种新兴的癌症细胞疗法和抗肿瘤免疫的有效介质。细胞因子诱导的记忆样（ML）NK细胞治疗是安全的，并诱导急性髓性白血病（AML）患者的缓解。然而，NK细胞转移后发生的影响患者结局的表型动态变化仍不清楚。在这里，我们使用质谱细胞术报告了ML NK细胞治疗的AML患者的全面多维相关性。这些数据鉴定了与常规NK细胞不同的独特的体内分化的ML NK细胞表型。此外，抑制性受体NKG2A是一种显性的、转录诱导的检查点，对ML很重要，但对癌症的常规NK细胞应答却不重要。CD8α+供体NK细胞频率与ML NK治疗后AML患者结局呈负相关。因此，阐明供体ML NK细胞在体内的多维动力学揭示了对临床应答重要的关键因素，以及增强NK细胞治疗的新途径。
NK cells are an emerging cancer cellular therapy and potent mediators of anti-tumor immunity. Cytokine-induced memory-like (ML) NK cellular therapy is safe and induces remissions in acute myeloid leukemia (AML) patients. However, the dynamic changes in phenotype that occur after NK cell transfer that impact patient outcomes remain unclear. Here, we report comprehensive multidimensional correlates from ML NK cell-treated AML patients using mass cytometry. These data identify a unique in vivo differentiated ML NK cell phenotype distinct from conventional NK cells. Moreover, the inhibitory receptor NKG2A is a dominant, transcriptionally-induced checkpoint important for ML, but not conventional NK cell responses to cancer. The frequency of CD8α+ donor NK cells is negatively associated with AML patient outcomes after ML NK therapy. Thus, elucidating the multidimensional dynamics of donor ML NK cells in vivo revealed critical factors important for clinical response, and new avenues to enhance NK cell therapeutics.