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

Frontiers in Oncology

Oncology

Kyle A. Romine¹  Matthew Viehdorfer¹  Jeffrey W. Tyner²  Daniel Bottomly³  Shannon K. McWeeney³  Nicola Long⁴  William Yashar⁵ 

[1] Knight Cancer Institute, Oregon Health & Science University, Portland, OR, United States;Knight Cancer Institute, Oregon Health & Science University, Portland, OR, United States;Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR, United States;Knight Cancer Institute, Oregon Health & Science University, Portland, OR, United States;Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, United States;Knight Cancer Institute, Oregon Health & Science University, Portland, OR, United States;Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR, United States;Knight Cancer Institute, Oregon Health & Science University, Portland, OR, United States;School of Medicine, Oregon Health & Science University, Portland, OR, United States;

关键词: AML – acute myeloid leukemia;    immune therapeutics;    checkpoint inhibition therapy;    RNAseq analysis;    functional genomic data;   

DOI  :  10.3389/fonc.2023.1192829

 received in 2023-03-23, accepted in 2023-05-22,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionThe 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.MethodsHere 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.ResultsWe 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.DiscussionOur 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.

【 授权许可】

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Copyright © 2023 Romine, Bottomly, Yashar, Long, Viehdorfer, McWeeney and Tyner