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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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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author Tanmaya Atre
Gregor S. D. Reid
Gregor S. D. Reid
author_facet Tanmaya Atre
Gregor S. D. Reid
Gregor S. D. Reid
author_sort Tanmaya Atre
collection DOAJ
description 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.
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spelling doaj-art-8ef5290e63e249a5811ee04cc379bfe32025-08-20T03:12:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15311451531145T cell exhaustion in pediatric B-ALL: current knowledge and future perspectivesTanmaya Atre0Gregor S. D. Reid1Gregor S. D. Reid2Michael Cuccione Childhood Cancer Research Program, BC Children’s Hospital Research Institute, Vancouver, BC, CanadaMichael Cuccione Childhood Cancer Research Program, BC Children’s Hospital Research Institute, Vancouver, BC, CanadaDepartment of Pediatrics, University of British Columbia, Vancouver, BC, CanadaB-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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1531145/fullpediatric B cell precursor acute lymphoblastic leukemiaT cell exhaustion (Tex)bispecific T cell engager (BiTE)chimeric antigen receptor (CAR T)immune checkpoint inhibition
spellingShingle Tanmaya Atre
Gregor S. D. Reid
Gregor S. D. Reid
T cell exhaustion in pediatric B-ALL: current knowledge and future perspectives
Frontiers in Immunology
pediatric B cell precursor acute lymphoblastic leukemia
T cell exhaustion (Tex)
bispecific T cell engager (BiTE)
chimeric antigen receptor (CAR T)
immune checkpoint inhibition
title T cell exhaustion in pediatric B-ALL: current knowledge and future perspectives
title_full T cell exhaustion in pediatric B-ALL: current knowledge and future perspectives
title_fullStr T cell exhaustion in pediatric B-ALL: current knowledge and future perspectives
title_full_unstemmed T cell exhaustion in pediatric B-ALL: current knowledge and future perspectives
title_short T cell exhaustion in pediatric B-ALL: current knowledge and future perspectives
title_sort t cell exhaustion in pediatric b all current knowledge and future perspectives
topic pediatric B cell precursor acute lymphoblastic leukemia
T cell exhaustion (Tex)
bispecific T cell engager (BiTE)
chimeric antigen receptor (CAR T)
immune checkpoint inhibition
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1531145/full
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