T cell exhaustion in pediatric B-ALL: current knowledge and future perspectives

B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric malignancy, accounting for 20-25% of all new cancer diagnoses in North American children each year. The leukemia arises, most commonly after a latency of 3–5 years, from a preleukemic B cell precursor population generated in ut...

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Bibliographic Details
Main Authors: Tanmaya Atre, Gregor S. D. Reid
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1531145/full
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Summary:B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric malignancy, accounting for 20-25% of all new cancer diagnoses in North American children each year. The leukemia arises, most commonly after a latency of 3–5 years, from a preleukemic B cell precursor population generated in utero. Despite the generally low immunogenicity of B-ALL cells, emerging evidence implicates T cell exhaustion - a state marked by sustained expression of inhibitory receptors and progressive functional decline - as a contributor to disease progression. Expression of inhibitory receptors is frequently detected on T cells from children with B-ALL at diagnosis and during therapy. As T cell exhaustion presents an actionable target for enhancing protective immune activity, in this review we summarize evidence from both clinical and pre-clinical settings for T cell exhaustion during pediatric B-ALL progression and discuss the opportunities and challenges to incorporating immune checkpoint blockade into pediatric B-ALL therapy regimens.
ISSN:1664-3224