A multidimensional analysis reveals distinct immune phenotypes and tertiary lymphoid structure-like aggregates in the bone marrow of pediatric acute myeloid leukemia

Because of the low mutational burden, children with acute myeloid leukemia (AML) are thought to have a 'cold' tumor microenvironment and consequently, a low likelihood of response to T cell-directed immunotherapies. Here, we provide a multidimensional overview of the tumor immune microenvi...

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Published inmedRxiv : the preprint server for health sciences
Main Authors Koedijk, Joost B, van der Werf, Inge, Penter, Livius, Vermeulen, Marijn A, Barneh, Farnaz, Perzolli, Alicia, Meesters-Ensing, Joyce I, Fiocco, Marta, de Groot-Kruseman, Hester A, Moeniralam, Rubina, Christensen, Kristina Bang, Porter, Billie, Pfaff, Kathleen, Garcia, Jacqueline S, Rodig, Scott J, Wu, Catherine J, Hasle, Henrik, Nierkens, Stefan, Belderbos, Mirjam E, Zwaan, C Michel, Heidenreich, Olaf
Format Journal Article
LanguageEnglish
Published United States 30.10.2023
Subjects
hematological malignancies
ectopic T cell networks
trephine
spatial transcriptomics
tertiary lymphoid structures
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Summary:Because of the low mutational burden, children with acute myeloid leukemia (AML) are thought to have a 'cold' tumor microenvironment and consequently, a low likelihood of response to T cell-directed immunotherapies. Here, we provide a multidimensional overview of the tumor immune microenvironment in newly diagnosed pediatric AML. On a cohort level, we demonstrate wide variation in T cell infiltration with nearly one-third of cases harboring an immune-infiltrated bone marrow. These immune-infiltrated cases are characterized by a decreased abundance of M2-like macrophages, which we find to be associated with response to T cell-directed immunotherapy in adult AML. On an organizational level, we reveal the composition of spatially organized immune aggregates in pediatric AML, and show that in the adult setting such aggregates in post-treatment bone marrow and extramedullary sites associate with response to ipilimumab-based therapy. Altogether, our study provides immune correlates of response to T cell-directed immunotherapies and indicates starting points for further investigations into immunomodulatory mechanisms in AML.