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000292501 1001_ $$00000-0001-6463-3307$$aKoedijk, Joost B$$b0
000292501 245__ $$aA multidimensional analysis reveals distinct immune phenotypes and the composition of immune aggregates in pediatric acute myeloid leukemia.
000292501 260__ $$aLondon$$bSpringer Nature$$c2024
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000292501 500__ $$a2024 Nov;38(11):2332-2343
000292501 520__ $$aBecause of the low mutational burden and consequently, fewer potential neoantigens, children with acute myeloid leukemia (AML) are thought to have a T cell-depleted or 'cold' tumor microenvironment and may have a low likelihood of response to T cell-directed immunotherapies. Understanding the composition, phenotype, and spatial organization of T cells and other microenvironmental populations in the pediatric AML bone marrow (BM) is essential for informing future immunotherapeutic trials about targetable immune-evasion mechanisms specific to pediatric AML. Here, we conducted a multidimensional analysis of the tumor immune microenvironment in pediatric AML and non-leukemic controls. We demonstrated that nearly one-third of pediatric AML cases has an immune-infiltrated BM, which is characterized by a decreased ratio of M2- to M1-like macrophages. Furthermore, we detected the presence of large T cell networks, both with and without colocalizing B cells, in the BM and dissected the cellular composition of T- and B cell-rich aggregates using spatial transcriptomics. These analyses revealed that these aggregates are hotspots of CD8+ T cells, memory B cells, plasma cells and/or plasmablasts, and M1-like macrophages. Collectively, our study provides a multidimensional characterization of the BM immune microenvironment in pediatric AML and indicates starting points for further investigations into immunomodulatory mechanisms in this devastating disease.
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000292501 7001_ $$avan der Werf, Inge$$b1
000292501 7001_ $$00000-0002-9060-0207$$aPenter, Livius$$b2
000292501 7001_ $$aVermeulen, Marijn A$$b3
000292501 7001_ $$aBarneh, Farnaz$$b4
000292501 7001_ $$00000-0003-1302-0943$$aPerzolli, Alicia$$b5
000292501 7001_ $$00000-0003-0780-9227$$aMeesters-Ensing, Joyce I$$b6
000292501 7001_ $$0P:(DE-He78)eab13a5d37ded394a30e8cef0c57b906$$aMetselaar, Dennis S$$b7
000292501 7001_ $$aMargaritis, Thanasis$$b8
000292501 7001_ $$aFiocco, Marta$$b9
000292501 7001_ $$ade Groot-Kruseman, Hester A$$b10
000292501 7001_ $$aMoeniralam, Rubina$$b11
000292501 7001_ $$aBang Christensen, Kristina$$b12
000292501 7001_ $$aPorter, Billie$$b13
000292501 7001_ $$aPfaff, Kathleen$$b14
000292501 7001_ $$00000-0003-2118-6302$$aGarcia, Jacqueline S$$b15
000292501 7001_ $$aRodig, Scott J$$b16
000292501 7001_ $$00000-0002-3348-5054$$aWu, Catherine J$$b17
000292501 7001_ $$00000-0003-3976-9231$$aHasle, Henrik$$b18
000292501 7001_ $$aNierkens, Stefan$$b19
000292501 7001_ $$00000-0002-6164-2918$$aBelderbos, Mirjam E$$b20
000292501 7001_ $$00000-0001-6892-8268$$aZwaan, C Michel$$b21
000292501 7001_ $$00000-0001-5404-6483$$aHeidenreich, Olaf$$b22
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