Risk-associated alterations in marrow T cells in pediatric leukemia

JCI Insight. 2020 Aug 20;5(16):e140179. doi: 10.1172/jci.insight.140179.


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 depletion of naive T cells and accumulation of terminal-effector T cells may contribute to the biologic basis of disease risk. Properties of immune microenvironment identified here may also impact optimal application of immune therapies, including T cell-redirection approaches in childhood leukemia.

Keywords: Immunology; Leukemias; T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Bone Marrow / pathology*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Gene Expression Profiling
  • Humans
  • Infant
  • Killer Cells, Natural / pathology
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / pathology*
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • Reproducibility of Results
  • Risk Factors
  • Single-Cell Analysis
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology*
  • Tumor Microenvironment / immunology*