Evidence map›Paper›PMID 41889837›Full record

ArticlebioRxiv : the preprint server for biology2026

Early microglial activation in the TME enables FLASH-RT to eradicate medulloblastoma while promoting neuron-astrocyte crosstalk to minimize toxicity in the hippocampus.

Michèle Knol, Javier Franco-Pérez, Aymeric Almeida, Louis V Kunz, Benoit Petit, Antoine Job, Jonathan Ollivier, Jackeline Romero, Jeannette Jansen, Veljko Grilj and 3 more

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Michèle KnolLiRR - Laboratory of Innovation in Radiobiology Applied to Radiotherapy/Faculty of Medicine/University of Geneva, Geneva, Switzerland.
Javier Franco-PérezLaboratorio Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía MVS, Mexico City, Mexico.
Aymeric AlmeidaLiRR - Laboratory of Innovation in Radiobiology Applied to Radiotherapy/Faculty of Medicine/University of Geneva, Geneva, Switzerland.
Louis V KunzLiRR - Laboratory of Innovation in Radiobiology Applied to Radiotherapy/Faculty of Medicine/University of Geneva, Geneva, Switzerland.
Benoit PetitLiRR - Laboratory of Innovation in Radiobiology Applied to Radiotherapy/Faculty of Medicine/University of Geneva, Geneva, Switzerland.
Antoine JobLiRR - Laboratory of Innovation in Radiobiology Applied to Radiotherapy/Faculty of Medicine/University of Geneva, Geneva, Switzerland.
Jonathan OllivierLiRR - Laboratory of Innovation in Radiobiology Applied to Radiotherapy/Faculty of Medicine/University of Geneva, Geneva, Switzerland.
Jackeline RomeroFormer affiliation: Laboratory of Radiation Oncology/Radiation Oncology Service/Department of Oncology/CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Jeannette JansenFormer affiliation: Laboratory of Radiation Oncology/Radiation Oncology Service/Department of Oncology/CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Veljko GriljInstitute of Radiation Physics (IRA)/CHUV, Lausanne University Hospital, Lausanne, Switzerland.
Charles LimoliDepartment of Radiation Oncology, University of California, Irvine, CA. USA.
Marie-Catherine VozeninLiRR - Laboratory of Innovation in Radiobiology Applied to Radiotherapy/Faculty of Medicine/University of Geneva, Geneva, Switzerland.ORCID 0000-0002-2109-8073
Paola Ballesteros-ZebadúaFormer affiliation: Laboratory of Radiation Oncology/Radiation Oncology Service/Department of Oncology/CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.ORCID 0000-0003-1263-2163

Funding

Project 4: Mechanistic Basics of FLASH Effect: Role of O2P01CA244091 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI LIMOLI, CHARLES · 2020 to 2024
$9.6M
Improving pediatric brain tumor treatments using FLASH radiotherapyR01CA254892 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Charles Limoli · 2021 to 2026
$2.5M
NCI NIH HHS P01 CA244091NCI NIH HHS R01 CA254892
6 · The paper itself

Abstract

Background: FLASH-RT defines a promising treatment modality against medulloblastoma, as it minimizes treatment-related complications. To support its clinical translation, we dissected the cellular and molecular determinants of the FLASH response in the tumor-microenvironment (TME) and healthy hippocampus using an orthotopic human medulloblastoma mouse model treated with a hypo-fractionated FLASH regimen. Methods: Five cohorts of 4 weeks-old UW228-MB-bearing female nude mice (n=57) were irradiated, or sham-irradiated using 3×10 Gy (BED=60), delivered 48h apart at 0.1 Gy/s (CONV) or 5.5×10 Results: Both CONV and FLASH-RT induced a complete and long-lasting anti-tumor response in 100% of animals associated with cognitive decline. However, more mice maintained a very good discrimination score after FLASH exposure (38%) than CONV (7%). DSP revealed a sustained microglial activation in the cerebellar tumor micro-environment, where FLASH enhanced expression of genes with phagocytic and proteolytic activity. In the tumor free hippocampus, FLASH exposure induced a preferential neuron/astrocyte transcriptional crosstalk, which manifested over protracted times to minimize neuroinflammation and cognitive complications. Conclusion: The study shows the tumor-ablative efficacy of hypo-fractionated FLASH-RT in a human medulloblastoma mouse model. It is associated with qualitatively distinct transcriptional signatures prone to tumor and debris clearance mediated by microglial cells of the TME. Moreover, in the hippocampus, FLASH mitigates radiation-induced neurotoxicity by enhancing genes involved in synaptic plasticity, attenuating neuroinflammation, and preserving metabolic function.

Indexed as

FLASHMedulloblastomaMicroglial activationNeuroinflammationNeuron-Astrocyte axis

Identifiers

PMID41889837
PMCPMC13015341

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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.