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Lookup NU author(s): Professor Olaf Heidenreich
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2024.Because of the low mutational burden and consequently, fewer potential neoantigens, children with acute myeloid leukemia (AML) are thought to have a T cell-depleted or ‘cold’ tumor microenvironment and may have a low likelihood of response to T cell-directed immunotherapies. Understanding the composition, phenotype, and spatial organization of T cells and other microenvironmental populations in the pediatric AML bone marrow (BM) is essential for informing future immunotherapeutic trials about targetable immune-evasion mechanisms specific to pediatric AML. Here, we conducted a multidimensional analysis of the tumor immune microenvironment in pediatric AML and non-leukemic controls. We demonstrated that nearly one-third of pediatric AML cases has an immune-infiltrated BM, which is characterized by a decreased ratio of M2- to M1-like macrophages. Furthermore, we detected the presence of large T cell networks, both with and without colocalizing B cells, in the BM and dissected the cellular composition of T- and B cell-rich aggregates using spatial transcriptomics. These analyses revealed that these aggregates are hotspots of CD8+ T cells, memory B cells, plasma cells and/or plasmablasts, and M1-like macrophages. Collectively, our study provides a multidimensional characterization of the BM immune microenvironment in pediatric AML and indicates starting points for further investigations into immunomodulatory mechanisms in this devastating disease.
Author(s): Koedijk JB, van der Werf I, Penter L, Vermeulen MA, Barneh F, Perzolli A, Meesters-Ensing JI, Metselaar DS, Margaritis T, Fiocco M, de Groot-Kruseman HA, Moeniralam R, Bang Christensen K, Porter B, Pfaff K, Garcia JS, Rodig SJ, Wu CJ, Hasle H, Nierkens S, Belderbos ME, Zwaan CM, Heidenreich O
Publication type: Article
Publication status: Published
Journal: Leukemia
Year: 2024
Pages: epub ahead of print
Online publication date: 26/08/2024
Acceptance date: 13/08/2024
Date deposited: 02/09/2024
ISSN (print): 0887-6924
ISSN (electronic): 1476-5551
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41375-024-02381-w
DOI: 10.1038/s41375-024-02381-w
Data Access Statement: Normalized sequencing data can be accessed from the Gene Expression Omnibus (nCounter data: GSE228481; GeoMx data: GSE248597). Requests for raw sequencing data should be addressed to and will be fulfilled by the corresponding author (OH).
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