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A multidimensional analysis reveals distinct immune phenotypes and the composition of immune aggregates in pediatric acute myeloid leukemia.
Koedijk, Joost B; van der Werf, Inge; Penter, Livius; Vermeulen, Marijn A; Barneh, Farnaz; Perzolli, Alicia; Meesters-Ensing, Joyce I; Metselaar, Dennis S; Margaritis, Thanasis; Fiocco, Marta; de Groot-Kruseman, Hester A; Moeniralam, Rubina; Bang Christensen, Kristina; 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.
Afiliación
  • Koedijk JB; Princess Máxima Center for Pediatric Oncology, 3584 CS, Utrecht, The Netherlands.
  • van der Werf I; Department of Pediatric Oncology, Erasmus MC/Sophia Children's Hospital, 3015 GD, Rotterdam, The Netherlands.
  • Penter L; Princess Máxima Center for Pediatric Oncology, 3584 CS, Utrecht, The Netherlands.
  • Vermeulen MA; Oncode Institute, 3521 AL, Utrecht, The Netherlands.
  • Barneh F; Sanford Stem Cell Institute, Division of Regenerative Medicine, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
  • Perzolli A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Meesters-Ensing JI; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
  • Metselaar DS; Harvard Medical School, Boston, MA, USA.
  • Margaritis T; Department of Hematology, Oncology, and Cancer Immunology, Campus Virchow Klinikum, Berlin, Germany.
  • Fiocco M; Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • de Groot-Kruseman HA; German Cancer Consortium (DKTK), partner site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Moeniralam R; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, BIH Charité Digital Clinician Scientist Program, Charitéplatz 1, 10117, Berlin, Germany.
  • Bang Christensen K; Princess Máxima Center for Pediatric Oncology, 3584 CS, Utrecht, The Netherlands.
  • Porter B; Princess Máxima Center for Pediatric Oncology, 3584 CS, Utrecht, The Netherlands.
  • Pfaff K; Princess Máxima Center for Pediatric Oncology, 3584 CS, Utrecht, The Netherlands.
  • Garcia JS; Department of Pediatric Oncology, Erasmus MC/Sophia Children's Hospital, 3015 GD, Rotterdam, The Netherlands.
  • Rodig SJ; Princess Máxima Center for Pediatric Oncology, 3584 CS, Utrecht, The Netherlands.
  • Wu CJ; Princess Máxima Center for Pediatric Oncology, 3584 CS, Utrecht, The Netherlands.
  • Hasle H; Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
  • Nierkens S; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Consortium (DKTK), Im Neuenheimer Feld 280, Heidelberg, Germany.
  • Belderbos ME; Princess Máxima Center for Pediatric Oncology, 3584 CS, Utrecht, The Netherlands.
  • Zwaan CM; Princess Máxima Center for Pediatric Oncology, 3584 CS, Utrecht, The Netherlands.
  • Heidenreich O; Mathematical Institute, Leiden University, Leiden, The Netherlands.
Leukemia ; 2024 Aug 26.
Article en En | MEDLINE | ID: mdl-39187578
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Leukemia Asunto de la revista: HEMATOLOGIA / NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Leukemia Asunto de la revista: HEMATOLOGIA / NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido