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| Status |
Public on Aug 27, 2024 |
| Title |
A multidimensional analysis reveals distinct immune phenotypes and tertiary lymphoid structure-like aggregates in pediatric acute myeloid leukemia. |
| Organism |
Homo sapiens |
| Experiment type |
Other
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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.
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| Overall design |
The aim of this spatial transcriptomics experiment was to compare the gene expression profiles of immune aggregates (large T cell networks that colocalized with a dense network of B cells; called Aggregate-regions) with mixed regions (containing AML cells and other microenvironmental populations; called MIXED1 in case this mixed region was from a biopsy that contained immune aggregates, and MIXED2 if the mixed region was from a biopsy that did not contain immune aggregates) and control regions (regions from non-leukemic control samples). In total, we sequenced regions from 4 AML biopsies with immune aggregates, 2 AML biopsies without immune aggregates, and 2 non-leukemic control biopsies. The number of regions successfully sequenced and for further details, we refer to our preprint on medRxiv: https://www.medrxiv.org/content/10.1101/2023.03.03.23286485v3.
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Submitter states that missing raw data are being made available for controlled access in EGA.
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| Contributor(s) |
Koedijk J, Heidenreich O |
| Citation(s) |
39187578 |
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| Submission date |
Nov 24, 2023 |
| Last update date |
Aug 27, 2024 |
| Contact name |
Joost Koedijk |
| E-mail(s) |
j.b.koedijk@prinsesmaximacentrum.nl
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| Organization name |
Princess Máxima Center for Pediatric Oncology
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| Street address |
Heidelberglaan 25
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| City |
Utrecht |
| ZIP/Postal code |
3584 CS |
| Country |
Netherlands |
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| Platforms (1) |
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| Samples (143)
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| Relations |
| BioProject |
PRJNA1044824 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE248597_Q3.normalized.counts.for.GEO.xlsx |
8.9 Mb |
(ftp)(http) |
XLSX |
| Raw data not provided for this record |
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