Journal Article

DKFZ-2024-01748

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A multidimensional analysis reveals distinct immune phenotypes and the composition of immune aggregates in pediatric acute myeloid leukemia.

Koedijk, J. B. ; van der Werf, I. ; Penter, L.DKFZ* ; Vermeulen, M. A. ; Barneh, F. ; Perzolli, A. ; Meesters-Ensing, J. I. ; Metselaar, D. S.DKFZ* ; Margaritis, T. ; Fiocco, M. ; de Groot-Kruseman, H. A. ; Moeniralam, R. ; Bang Christensen, K. ; Porter, B. ; Pfaff, K. ; Garcia, J. S. ; Rodig, S. J. ; Wu, C. J. ; Hasle, H. ; Nierkens, S. ; Belderbos, M. E. ; Zwaan, C. M. ; Heidenreich, O.

2024
Springer Nature London

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Please use a persistent id in citations: doi:10.1038/s41375-024-02381-w

Abstract: 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.

Note: 2024 Nov;38(11):2332-2343

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Contributing Institute(s):

1. B062 Pädiatrische Neuroonkologie (B062)
2. DKTK HD zentral (HD01)
3. DKTK Koordinierungsstelle Berlin (BE01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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