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@ARTICLE{Koedijk:292501,
author = {J. B. Koedijk and I. van der Werf and L. Penter$^*$ and M.
A. Vermeulen and F. Barneh and A. Perzolli and J. I.
Meesters-Ensing and D. S. Metselaar$^*$ and T. Margaritis
and M. Fiocco and H. A. de Groot-Kruseman and R. Moeniralam
and K. Bang Christensen and B. Porter and K. Pfaff and J. S.
Garcia and S. J. Rodig and C. J. Wu and H. Hasle and S.
Nierkens and M. E. Belderbos and C. M. Zwaan and O.
Heidenreich},
title = {{A} multidimensional analysis reveals distinct immune
phenotypes and the composition of immune aggregates in
pediatric acute myeloid leukemia.},
journal = {Leukemia},
volume = {38},
number = {11},
issn = {0887-6924},
address = {London},
publisher = {Springer Nature},
reportid = {DKFZ-2024-01748},
pages = {2332-2343},
year = {2024},
note = {2024 Nov;38(11):2332-2343},
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.},
cin = {B062 / HD01 / BE01},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)BE01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39187578},
doi = {10.1038/s41375-024-02381-w},
url = {https://inrepo02.dkfz.de/record/292501},
}