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Record W4401514101 · doi:10.1016/j.cell.2024.07.030

Macrophage-mediated myelin recycling fuels brain cancer malignancy

2024· article· en· W4401514101 on OpenAlex
Daan J. Kloosterman, Johanna Erbani, Menno Boon, Martina Farber, Shanna M. Handgraaf, Masami Ando‐Kuri, Elena Sánchez‐López, Bauke Fontein, Marjolijn Mertz, Marja Nieuwland, Ning Qing Liu, Gabriel Forn‐Cuní, Nicole N. van der Wel, Anita E. Grootemaat, Luuk Reinalda, Sander I. van Kasteren, Elzo de Wit, Brian Ruffell, B. Ewa Snaar‐Jagalska, Kevin Petrecca, Dieta Brandsma, Alexander Kros, Martin Giera, Leila Akkari

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueCell · 2024
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmune cells in cancer
Canadian institutionsMcGill University Health Centre
FundersH2020 European Research CouncilEuropean Research CouncilAard- en Levenswetenschappen, Nederlandse Organisatie voor Wetenschappelijk OnderzoekKWF KankerbestrijdingOncode InstituteNederlandse Organisatie voor Wetenschappelijk OnderzoekCancer Genomics Centre
KeywordsBiologyTumor microenvironmentCrosstalkCancer researchMyelinImmune systemMacrophageMicrovesiclesMicrogliaMesenchymal stem cellGlioblastomaPhenotypeImmunologyNeuroscienceCell biologyGeneticsGeneCentral nervous systemInflammationmicroRNAIn vitro

Abstract

fetched live from OpenAlex

Tumors growing in metabolically challenged environments, such as glioblastoma in the brain, are particularly reliant on crosstalk with their tumor microenvironment (TME) to satisfy their high energetic needs. To study the intricacies of this metabolic interplay, we interrogated the heterogeneity of the glioblastoma TME using single-cell and multi-omics analyses and identified metabolically rewired tumor-associated macrophage (TAM) subpopulations with pro-tumorigenic properties. These TAM subsets, termed lipid-laden macrophages (LLMs) to reflect their cholesterol accumulation, are epigenetically rewired, display immunosuppressive features, and are enriched in the aggressive mesenchymal glioblastoma subtype. Engulfment of cholesterol-rich myelin debris endows subsets of TAMs to acquire an LLM phenotype. Subsequently, LLMs directly transfer myelin-derived lipids to cancer cells in an LXR/Abca1-dependent manner, thereby fueling the heightened metabolic demands of mesenchymal glioblastoma. Our work provides an in-depth understanding of the immune-metabolic interplay during glioblastoma progression, thereby laying a framework to unveil targetable metabolic vulnerabilities in glioblastoma.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
Consensus categoriesInsufficient payload (model declined to judge)
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.636
Threshold uncertainty score0.991

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0100.010

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.011
GPT teacher head0.262
Teacher spread0.251 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Quick stats

Citations187
Published2024
Admission routes1
Has abstractyes

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