Immune cell proportions correlate with clinicogenomic features and ex vivo drug responses in acute myeloid leukemia.
Immune cell proportions correlate with clinicogenomic features and ex vivo drug responses in acute myeloid leukemia.
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DOI：
10.3389/fonc.2023.1192829
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发表时间：
2023
影响因子：
4.7
通讯作者：
Tyner, Jeffrey W.
中科院分区：
文献类型：
--
作者：
Romine, Kyle A.;Bottomly, Daniel;Yashar, William;Long, Nicola;Viehdorfer, Matthew;McWeeney, Shannon K.;Tyner, Jeffrey W.
关键词：
由于患者之间的遗传和表观遗传变异性，在急性髓性白血病（AML）中实施小分子和免疫疗法一直具有挑战性。免疫细胞可以影响小分子或免疫治疗反应的潜在机制有很多，但这一领域的研究仍然不足。在这里，我们对来自Beat AML数据集的560多个AML患者骨髓和外周血样本进行了细胞类型富集分析，以描述AML的功能性免疫景观。我们鉴定了与AML临床和遗传特征显著相关的多种细胞类型，我们还观察到免疫细胞比例与离体小分子和免疫治疗反应的显著相关性。此外，我们产生了终末耗竭T细胞（Tex）的特征，并将具有高单核细胞比例的AML鉴定为与这些免疫抑制性T细胞的比例增加密切相关。我们的工作可以通过我们可视化平台（Vizome; http：//vizome.org/）中的新“细胞类型”模块访问，可以用来研究不同免疫细胞对AML生物学许多方面的潜在贡献。
The implementation of small-molecule and immunotherapies in acute myeloid leukemia (AML) has been challenging due to genetic and epigenetic variability amongst patients. There are many potential mechanisms by which immune cells could influence small-molecule or immunotherapy responses, yet, this area remains understudied. Here we performed cell type enrichment analysis from over 560 AML patient bone marrow and peripheral blood samples from the Beat AML dataset to describe the functional immune landscape of AML. We identify multiple cell types that significantly correlate with AML clinical and genetic features, and we also observe significant correlations of immune cell proportions with ex vivo small-molecule and immunotherapy responses. Additionally, we generated a signature of terminally exhausted T cells (Tex) and identified AML with high monocytic proportions as strongly correlating with increased proportions of these immunosuppressive T cells. Our work, which is accessible through a new “Cell Type” module in our visualization platform (Vizome; http://vizome.org/), can be leveraged to investigate potential contributions of different immune cells on many facets of the biology of AML.
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影响因子：
64.8
作者：
Tyner JW;Tognon CE;Bottomly D;Wilmot B;Kurtz SE;Savage SL;Long N;Schultz AR;Traer E;Abel M;Agarwal A;Blucher A;Borate U;Bryant J;Burke R;Carlos A;Carpenter R;Carroll J;Chang BH;Coblentz C;d'Almeida A;Cook R;Danilov A;Dao KT;Degnin M;Devine D;Dibb J;Edwards DK 5th;Eide CA;English I;Glover J;Henson R;Ho H;Jemal A;Johnson K;Johnson R;Junio B;Kaempf A;Leonard J;Lin C;Liu SQ;Lo P;Loriaux MM;Luty S;Macey T;MacManiman J;Martinez J;Mori M;Nelson D;Nichols C;Peters J;Ramsdill J;Rofelty A;Schuff R;Searles R;Segerdell E;Smith RL;Spurgeon SE;Sweeney T;Thapa A;Visser C;Wagner J;Watanabe-Smith K;Werth K;Wolf J;White L;Yates A;Zhang H;Cogle CR;Collins RH;Connolly DC;Deininger MW;Drusbosky L;Hourigan CS;Jordan CT;Kropf P;Lin TL;Martinez ME;Medeiros BC;Pallapati RR;Pollyea DA;Swords RT;Watts JM;Weir SJ;Wiest DL;Winters RM;McWeeney SK;Druker BJ
通讯作者：
Druker BJ
PD-1和PD-L1检查点信号传导抑制癌症免疫疗法：机制，组合和临床结果。
影响因子：
5.6
作者：
Alsaab HO;Sau S;Alzhrani R;Tatiparti K;Bhise K;Kashaw SK;Iyer AK
通讯作者：
Iyer AK
影响因子：
64.8
作者：
Im SJ;Hashimoto M;Gerner MY;Lee J;Kissick HT;Burger MC;Shan Q;Hale JS;Lee J;Nasti TH;Sharpe AH;Freeman GJ;Germain RN;Nakaya HI;Xue HH;Ahmed R
通讯作者：
Ahmed R
影响因子：
8.8
作者：
Jenkins RW;Barbie DA;Flaherty KT
通讯作者：
Flaherty KT
影响因子：
10.1
作者：
Kuusanmaki, Heikki;Leppa, Aino-Maija;Heckman, Caroline A.
通讯作者：
Heckman, Caroline A.