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Record W2774491730 · doi:10.1080/2162402x.2017.1412909

Glioblastoma stem cell-derived exosomes induce M2 macrophages and PD-L1 expression on human monocytes

2017· article· en· W2774491730 on OpenAlexaff
Konrad Gabrusiewicz, Xu Li, Jun Wei, Yuuri Hashimoto, Anantha Marisetty, Martina Ott, Fei Wang, David H. Hawke, Jun Yu, Luke M. Healy, Anwar Hossain, Johnny Akers, Sourindra N. Maiti, Shinji Yamashita, Yuzaburo Shimizu, Kenneth Dunner, Malgorzata Anna Zal, Jared K. Burks, Joy Gumin, Felix Nwajei, Aras Rezavanian, Shouhao Zhou, Ganesh Rao, Raymond Sawaya, Gregory N. Fuller, Jason T. Huse, Jack P. Antel, Shulin Li, Laurence J.N. Cooper, Erik P. Sulman, Clark C. Chen, Changiz Geula, Raghu Kalluri, Tomasz Żal, Amy B. Heimberger

Bibliographic record

VenueOncoImmunology · 2017
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicExtracellular vesicles in disease
Canadian institutionsMcGill UniversityMontreal Neurological Institute and Hospital
FundersNational Center for Research ResourcesNational Institute of Neurological Disorders and StrokeNational Cancer InstituteNational Institutes of HealthCancer Prevention and Research Institute of Texas
KeywordsMicrovesiclesBiologyImmune systemSTAT proteinCancer researchSTAT3Cell biologyCD14ExosomeTumor microenvironmentPhosphorylationImmunologymicroRNA

Abstract

fetched live from OpenAlex

Exosomes can mediate a dynamic method of communication between malignancies, including those sequestered in the central nervous system and the immune system. We sought to determine whether exosomes from glioblastoma (GBM)-derived stem cells (GSCs) can induce immunosuppression. We report that GSC-derived exosomes (GDEs) have a predilection for monocytes, the precursor to macrophages. The GDEs traverse the monocyte cytoplasm, cause a reorganization of the actin cytoskeleton, and skew monocytes toward the immune suppresive M2 phenotype, including programmed death-ligand 1 (PD-L1) expression. Mass spectrometry analysis demonstrated that the GDEs contain a variety of components, including members of the signal transducer and activator of transcription 3 (STAT3) pathway that functionally mediate this immune suppressive switch. Western blot analysis revealed that upregulation of PD-L1 in GSC exosome-treated monocytes and GBM-patient-infiltrating CD14+ cells predominantly correlates with increased phosphorylation of STAT3, and in some cases, with phosphorylated p70S6 kinase and Erk1/2. Cumulatively, these data indicate that GDEs are secreted GBM-released factors that are potent modulators of the GBM-associated immunosuppressive microenvironment.

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.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

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 integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.019
GPT teacher head0.290
Teacher spread0.271 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations365
Published2017
Admission routes1
Has abstractyes

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