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

GSE248287 Homo sapiens Other; Expression profiling by high throughput sequencing 34 samples Submitted 2025/07/25 Platform GPL18573
Summary
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-TCRab 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 novel (immuno)therapeutic targets and risk stratification for treatment.
Published in
Remodeling of the immune microenvironment is linked to adverse outcome in pediatric T cell acute lymphoblastic leukemia
Wiggers CRM, Cho EY, Ozdemir M et al. · Nature communications 2025 · PMID 41271691 · doi:10.1038/s41467-025-65134-y
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Direct links to NCBI, no account and no request form: the whole study as GSE248287_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 34 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1043165. Searching any of these in the dataset finder brings you back here.

Study design
34 conditions, each sampled once — no replicated groups

Read from 34 sample titles: 34 distinct titles with little repetition. Check it against the sample list below before relying on it.

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