Spatial analysis reveals distinct immune phenotypes and tertiary lymphoid structure-like aggregates in pediatric AML
Klinische Pädiatrie, vol. 235, pp. 197
Abstract
Pediatric cancers are characterized by a relatively low mutational burden and therefore, children are thought to be poor candidates for T cell-engaging immunotherapies. Here, we performed a multidimensional characterization of the tumor immune microenvironment in newly diagnosed children with acute myeloid leukemia (AML) and non-leukemic controls. We identified a subset of pediatric AML patients with remarkably high levels of T cell infiltration and a relatively low abundance of anti-inflammatory macrophages in the bone marrow. In addition, we detected large T cell networks that colocalized with B cells in immune-infiltrated samples, resembling tertiary lymphoid structures as described in solid tumors. Using spatial transcriptomics, we dissected the composition of these structures and revealed unique hotspots of anti-tumor immunity. This work raises the possibility that a subset of pediatric AML patients may benefit from T cell-engaging immunotherapies and encourages further study of these lymphoid structures in the context of immunotherapy in AML. Publication History Article published online: 12 May 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany
Authors 10
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Princess Máxima Center · Erasmus MC - Sophia Children’s Hospital
Affiliation as printed
Department of Pediatric Oncology, Erasmus MC/Sophia Children's Hospital, 3015 GD Rotterdam, The Netherlands
Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands
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Oncode Institute · Princess Máxima Center
Affiliation as printed
Oncode Institute, 3521 AL, Utrecht, The Netherlands
Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands
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Affiliation as printed
Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands
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Princess Máxima Center · Erasmus MC - Sophia Children’s Hospital
Affiliation as printed
Department of Pediatric Oncology, Erasmus MC/Sophia Children's Hospital, 3015 GD Rotterdam, The Netherlands
Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands
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Leiden University · Leiden University Medical Center · Princess Máxima Center
Affiliation as printed
Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
Mathematical Institute, Leiden University, Leiden, The Netherlands
Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands
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Affiliation as printed
Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands
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University Medical Center Utrecht · Princess Máxima Center
Affiliation as printed
Center for Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands
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Affiliation as printed
Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands
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Princess Máxima Center · Erasmus MC - Sophia Children’s Hospital
Affiliation as printed
Department of Pediatric Oncology, Erasmus MC/Sophia Children's Hospital, 3015 GD Rotterdam, The Netherlands
Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands
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Princess Máxima Center · Newcastle University
Affiliation as printed
Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands
Wolfson Childhood Cancer Research Centre, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
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