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Record W4323856878 · doi:10.3389/fimmu.2023.1099459

Fatty acid transport protein inhibition sensitizes breast and ovarian cancers to oncolytic virus therapy via lipid modulation of the tumor microenvironment

2023· article· en· W4323856878 on OpenAlexafffund
Abera Surendran, Monire Jamalkhah, Joanna Poutou, Rayanna Birtch, Christine Lawson, Jaahnavi Dave, Mathieu J. F. Crupi, Justin Mayer, Victoria M. Taylor, Julia Petryk, Christiano Tanese de Souza, Neil Moodie, Jacob Lecompte Billingsley, Bradley Austin, Nicole Cormack, Natalie Blamey, Reza Rezaei, Curtis W. McCloskey, Emily E.F. Fekete, Harsimrat Kaur Birdi, Serge Neault, Taylor R. Jamieson, Brenna Wylie, Sarah Tucker, Taha Azad, Barbara C. Vanderhyden, Lee‐Hwa Tai, John C. Bell, Carolina S. Ilkow

Bibliographic record

VenueFrontiers in Immunology · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicVirus-based gene therapy research
Canadian institutionsUniversité de SherbrookeOttawa HospitalUniversity of Ottawa
FundersOttawa Hospital Research InstituteCanadian Cancer Society Research InstituteCanadian Institutes of Health ResearchCancer Research SocietyUniversity of Ottawa
KeywordsOncolytic virusAdipocyteTumor microenvironmentVirotherapyCancer researchAdipose tissueLipid dropletOvarian cancerCancerCancer cellBiologyLipid metabolismCell biologyInternal medicineEndocrinologyMedicineTumor cells

Abstract

fetched live from OpenAlex

Introduction: Adipocytes in the tumour microenvironment are highly dynamic cells that have an established role in tumour progression, but their impact on anti-cancer therapy resistance is becoming increasingly difficult to overlook. Methods: We investigated the role of adipose tissue and adipocytes in response to oncolytic virus (OV) therapy in adipose-rich tumours such as breast and ovarian neoplasms. Results: We show that secreted products in adipocyte-conditioned medium significantly impairs productive virus infection and OV-driven cell death. This effect was not due to the direct neutralization of virions or inhibition of OV entry into host cells. Instead, further investigation of adipocyte secreted factors demonstrated that adipocyte-mediated OV resistance is primarily a lipid-driven phenomenon. When lipid moieties are depleted from the adipocyte-conditioned medium, cancer cells are re-sensitized to OV-mediated destruction. We further demonstrated that blocking fatty acid uptake by cancer cells, in a combinatorial strategy with virotherapy, has clinical translational potential to overcome adipocyte-mediated OV resistance. Discussion: Our findings indicate that while adipocyte secreted factors can impede OV infection, the impairment of OV treatment efficacy can be overcome by modulating lipid flux in the tumour milieu.

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 head0.007
GPT teacher head0.228
Teacher spread0.221 · 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

Citations13
Published2023
Admission routes2
Has abstractyes

Explore more

Same venueFrontiers in Immunology→Same topicVirus-based gene therapy research→French-language works237,207→