Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Risk-associated alterations in marrow T cells in pediatric leukemia
Jithendra Kini Bailur, … , Madhav V. Dhodapkar, Kavita M. Dhodapkar
Jithendra Kini Bailur, … , Madhav V. Dhodapkar, Kavita M. Dhodapkar
Published July 21, 2020
Citation Information: JCI Insight. 2020;5(16):e140179. https://doi.org/10.1172/jci.insight.140179.
View: Text | PDF
Research Article Immunology

Risk-associated alterations in marrow T cells in pediatric leukemia

  • Text
  • PDF
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 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.

Authors

Jithendra Kini Bailur, Samuel S. McCachren, Katherine Pendleton, Juan C. Vasquez, Hong Seo Lim, Alyssa Duffy, Deon B. Doxie, Akhilesh Kaushal, Connor Foster, Deborah DeRyckere, Sharon Castellino, Melissa L. Kemp, Peng Qiu, Madhav V. Dhodapkar, Kavita M. Dhodapkar

×

Graphical abstract

Options: View larger image (or click on image)

Copyright © 2022 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts