Immune cell proportions correlate with clinicogenomic features and ex vivo drug responses in acute myeloid leukemia

被引:1
|
作者
Romine, Kyle A. [1 ]
Bottomly, Daniel [1 ,2 ]
Yashar, William [1 ,3 ]
Long, Nicola [1 ,4 ]
Viehdorfer, Matthew [1 ]
McWeeney, Shannon K. [1 ,2 ]
Tyner, Jeffrey W. [1 ,5 ]
机构
[1] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA
[2] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Div Bioinformat & Computat Biol, Portland, OR 97239 USA
[3] Oregon Hlth & Sci Univ, Sch Med, Portland, OR USA
[4] Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR USA
[5] Oregon Hlth & Sci Univ, Dept Cell Dev & Canc Biol, Portland, OR 97239 USA
来源
FRONTIERS IN ONCOLOGY | 2023年 / 13卷
关键词
AML - acute myeloid leukemia; immune therapeutics; checkpoint inhibition therapy; RNAseq analysis; functional genomic data; REGULATORY T-CELLS; GROWTH-FACTOR; SUPPRESSION; RESISTANCE;
D O I
10.3389/fonc.2023.1192829
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Introduction: 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. Methods: 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. Results: 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. Discussion: 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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页数:9
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