Remodeling of the immune microenvironment is linked to adverse outcome in pediatric T cell acute lymphoblastic leukemia

Caroline R. M. Wiggers, Eugene Y. Cho, Merve Ozdemir, Gbolahan Bamgbose, Justin Hegel, Julia Frede, Frederike Warlitz, Tayla B. Heavican-Foral, Ioana Pop, Rawan Shraim, Petri Pölönen, Victoria Koch, Thai Hoa Tran, Charles G. Mullighan, David T. Teachey, Jacob R. Bledsoe, Yana Pikman, Marian H. Harris, Andrew E. Place, Lewis B. Silverman, Jens G. Lohr () and Birgit Knoechel ()
Additional contact information
Caroline R. M. Wiggers: Dana-Farber Cancer Institute, Department of Pediatric Oncology
Eugene Y. Cho: Dana-Farber Cancer Institute, Department of Pediatric Oncology
Merve Ozdemir: Dana-Farber Cancer Institute, Department of Pediatric Oncology
Gbolahan Bamgbose: University of Utah, Huntsman Cancer Institute
Justin Hegel: Dana-Farber Cancer Institute, Department of Pediatric Oncology
Julia Frede: Harvard Medical School
Frederike Warlitz: Dana-Farber Cancer Institute, Department of Pediatric Oncology
Tayla B. Heavican-Foral: Dana-Farber Cancer Institute, Department of Pediatric Oncology
Ioana Pop: University of Utah, Huntsman Cancer Institute
Rawan Shraim: University of Pennsylvania Perelman School of Medicine, Division of Oncology, Department of Pediatrics, Children’s Hospital of Philadelphia
Petri Pölönen: St. Jude Children’s Research Hospital, Department of Pathology
Victoria Koch: Dana-Farber Cancer Institute, Department of Pediatric Oncology
Thai Hoa Tran: Centre Hospitalier Universitaire Sainte-Justine, Division of Pediatric Hematology-Oncology, Charles-Bruneau Cancer Center
Charles G. Mullighan: St. Jude Children’s Research Hospital, Department of Pathology
David T. Teachey: University of Pennsylvania Perelman School of Medicine, Division of Oncology, Department of Pediatrics, Children’s Hospital of Philadelphia
Jacob R. Bledsoe: Harvard Medical School, Department of Pathology, Boston Children’s Hospital
Yana Pikman: Dana-Farber Cancer Institute, Department of Pediatric Oncology
Marian H. Harris: Harvard Medical School, Department of Pathology, Boston Children’s Hospital
Andrew E. Place: Dana-Farber Cancer Institute, Department of Pediatric Oncology
Lewis B. Silverman: Columbia University Irving Medical Center, Division of Pediatric Hematology, Oncology and Stem Cell Transplantation
Jens G. Lohr: Harvard Medical School
Birgit Knoechel: Dana-Farber Cancer Institute, Department of Pediatric Oncology

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Changes in the immune microenvironment are frequent in cancers occurring in adult patients, yet our understanding of the pediatric cancer immune microenvironment and its clinical relevance is limited. We investigate the immune microenvironment in pediatric T cell acute lymphoblastic leukemia (T-ALL), using single-cell CITE-seq and immune repertoire analyses. We identify a T-ALL subgroup characterized by a remodeled immune microenvironment, which is associated with adverse clinical outcome in minimal residual disease low patients. This adverse immune landscape is dominated by the presence of a population of non-malignant CD4-CD8-TCRαβ T cells that interact with CXCL16 expressing non-classical monocytes. Leukemia cell intrinsic transcriptional rewiring in these patients is associated with activation of Rap1 signaling. Inhibiting Rap1 signaling results in increased sensitivity to the BCL2/BCL-XL inhibitor navitoclax. Our study provides insights into the immune microenvironment of pediatric hematologic malignancies, forming the basis for identifying potential (immuno) therapeutic targets and risk stratification for treatment.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-65134-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65134-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-65134-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().