TY  - JOUR
AU  - Koedijk, Joost B
AU  - van der Werf, Inge
AU  - Penter, Livius
AU  - Vermeulen, Marijn A
AU  - Barneh, Farnaz
AU  - Perzolli, Alicia
AU  - Meesters-Ensing, Joyce I
AU  - Metselaar, Dennis S
AU  - Margaritis, Thanasis
AU  - Fiocco, Marta
AU  - de Groot-Kruseman, Hester A
AU  - Moeniralam, Rubina
AU  - Bang Christensen, Kristina
AU  - Porter, Billie
AU  - Pfaff, Kathleen
AU  - Garcia, Jacqueline S
AU  - Rodig, Scott J
AU  - Wu, Catherine J
AU  - Hasle, Henrik
AU  - Nierkens, Stefan
AU  - Belderbos, Mirjam E
AU  - Zwaan, C Michel
AU  - Heidenreich, Olaf
TI  - A multidimensional analysis reveals distinct immune phenotypes and the composition of immune aggregates in pediatric acute myeloid leukemia.
JO  - Leukemia
VL  - 38
IS  - 11
SN  - 0887-6924
CY  - London
PB  - Springer Nature
M1  - DKFZ-2024-01748
SP  - 2332-2343
PY  - 2024
N1  - 2024 Nov;38(11):2332-2343
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:39187578
DO  - DOI:10.1038/s41375-024-02381-w
UR  - https://inrepo02.dkfz.de/record/292501
ER  -