%0 Journal Article
%A Koedijk, Joost B
%A van der Werf, Inge
%A Penter, Livius
%A Vermeulen, Marijn A
%A Barneh, Farnaz
%A Perzolli, Alicia
%A Meesters-Ensing, Joyce I
%A Metselaar, Dennis S
%A Margaritis, Thanasis
%A Fiocco, Marta
%A de Groot-Kruseman, Hester A
%A Moeniralam, Rubina
%A Bang Christensen, Kristina
%A Porter, Billie
%A Pfaff, Kathleen
%A Garcia, Jacqueline S
%A Rodig, Scott J
%A Wu, Catherine J
%A Hasle, Henrik
%A Nierkens, Stefan
%A Belderbos, Mirjam E
%A Zwaan, C Michel
%A Heidenreich, Olaf
%T A multidimensional analysis reveals distinct immune phenotypes and the composition of immune aggregates in pediatric acute myeloid leukemia.
%J Leukemia
%V 38
%N 11
%@ 0887-6924
%C London
%I Springer Nature
%M DKFZ-2024-01748
%P 2332-2343
%D 2024
%Z 2024 Nov;38(11):2332-2343
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:39187578
%R 10.1038/s41375-024-02381-w
%U https://inrepo02.dkfz.de/record/292501