Evidence map›Paper›PMID 40726212›Full record

ArticleNeuro-oncology2025

Multimodal analysis of pediatric pilocytic astrocytomas reveals tumor location-associated cellular and transcriptional heterogeneity.

Julie A S Lammers, Jacob S Rozowsky, Friso G Calkoen, Thijs J M van den Broek, Joyce I Meesters-Ensing, Tiago Carvalheiro, Tiago P J Rijsdijk, Robyn D Gartrell, Dannis G van Vuurden, Henk G Stunnenberg and 5 more

Abstract read
In one paragraph

Article in Neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Julie A S LammersPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Jacob S RozowskyPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Friso G CalkoenPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Thijs J M van den BroekPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Joyce I Meesters-EnsingPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Tiago CarvalheiroPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Tiago P J RijsdijkPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Robyn D GartrellDepartment of Oncology, Division of Pediatric Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Dannis G van VuurdenPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Henk G StunnenbergPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Eelco W HovingPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Pieter WesselingDepartment of Pathology, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
Jasper van der LugtPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Mariëtte E G KranendonkPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.ORCID 0000-0001-9683-7494
Lennart A KesterPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.ORCID 0000-0002-8259-9971

Funding

Princess Máxima Center for Pediatric Oncology
6 · The paper itself

Abstract

backgroundPilocytic astrocytomas (PAs) are the most common pediatric central nervous system tumors, which present with limited genetic but significant clinical heterogeneity. Current treatment strategies are partly effective, but tumors often progress, and patients experience long-term side effects, highlighting the need for additional novel therapeutic approaches. A promising alternative approach could be targeting the tumor immune microenvironment (TIME); however, a comprehensive overview of the TIME of PAs across different anatomical tumor locations is currently lacking. The aim of this study was to comprehensively characterize the cellular and transcriptional landscape of pediatric PAs.

methodsWe employed a multimodal, integrative approach using single-nucleus and bulk RNA-sequencing alongside high-dimensional immunofluorescence imaging and flow cytometry to elucidate the transcriptional landscape and cellular composition of pediatric PAs across tumor locations.

resultsOur analysis uncovered neoplastic cell transcriptional heterogeneity reflective of aberrant glial differentiation. Moreover, we provided a detailed characterization of the TIME, revealing pro-inflammatory brain-resident microglia and abundant activated monocyte-derived macrophages and T cells. Deconvolution of bulk RNA-sequencing data revealed variation in tumor and TIME composition across anatomical tumor locations. Suprasellar tumors additionally exhibited increased expression of immune-related genes compared to tumors arising in other anatomical locations.

conclusionsTogether, our multimodal in-depth characterization provides detailed insights into the transcriptional and cellular heterogeneity of pediatric PAs across distinct anatomical tumor locations, which could aid in the development of novel (immuno)therapeutic approaches.

Indexed as

AstrocytomaBiomarkers, TumorBrain NeoplasmsTumor MicroenvironmentAdolescentChildChild, PreschoolFemaleGenetic HeterogeneityHumansInfantMalePrognosisSingle-Cell AnalysisBiomarkers, Tumordeconvolutionpilocytic astrocytomasingle-nucleus RNA-sequencingtumor immune microenvironment

Identifiers

PMID40726212
PMCPMC12916743

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.