Risk-associated alterations in marrow T cells in pediatric leukemia.

JCI Insight
Jithendra Kini BailurKavita M Dhodapkar

Abstract

Current management of childhood leukemia is tailored based on disease risk determined by clinical features at presentation. Whether properties of the host immune response impact disease risk and outcome is not known. Here, we combine mass cytometry, single cell genomics, and functional studies to characterize the BM immune environment in children with B cell acute lymphoblastic leukemia and acute myelogenous leukemia at presentation. T cells in leukemia marrow demonstrate evidence of chronic immune activation and exhaustion/dysfunction, with attrition of naive T cells and TCF1+ stem-like memory T cells and accumulation of terminally differentiated effector T cells. Marrow-infiltrating NK cells also exhibit evidence of dysfunction, particularly in myeloid leukemia. Properties of immune cells identified distinct immune phenotype-based clusters correlating with disease risk in acute lymphoblastic leukemia. High-risk immune signatures were associated with expression of stem-like genes on tumor cells. These data provide a comprehensive assessment of the immune landscape of childhood leukemias and identify targets potentially amenable to therapeutic intervention. These studies also suggest that properties of the host response with de...Continue Reading

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Citations

Mar 16, 2021·Frontiers in Immunology·Samuel S McCachrenMadhav V Dhodapkar
Jul 25, 2021·Leukemia·Sarah TettamantiMarta Serafini

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Datasets Mentioned

BETA
GSE154109

Methods Mentioned

BETA
flow cytometry
scRNA-Seq
density gradient centrifugation
FCS

Software Mentioned

Seurat
R
GraphPad Prism
SPADE
Cytobank
SingleR
Cell Ranger
FlowJo

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