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Record W4281661351 · doi:10.3389/fonc.2022.841921

Eosinophils Decrease Pulmonary Metastatic Mammary Tumor Growth

2022· article· en· W4281661351 on OpenAlexafffund
Rachel A. Cederberg, S. Elizabeth Franks, Brennan J. Wadsworth, Alvina So, Lisa R. Decotret, Michael G. Hall, Rocky Shi, Michael R. Hughes, Kelly M. McNagny, Kevin L. Bennewith

Bibliographic record

VenueFrontiers in Oncology · 2022
Typearticle
Languageen
FieldMedicine
TopicAsthma and respiratory diseases
Canadian institutionsUniversity of British Columbia
FundersCanadian Institutes of Health ResearchCancer Research SocietyCancer Research Institute
KeywordsEosinophilEosinophil peroxidaseMetastatic breast cancerImmune systemMedicineImmunologyCancer researchMetastasisMammary tumorBiologyCancerBreast cancerPathologyInternal medicine

Abstract

fetched live from OpenAlex

Metastatic breast cancer is challenging to effectively treat, highlighting the need for an improved understanding of host factors that influence metastatic tumor cell colonization and growth in distant tissues. The lungs are a common site of breast cancer metastasis and are host to a population of tissue-resident eosinophils. Eosinophils are granulocytic innate immune cells known for their prominent roles in allergy and Th2 immunity. Though their presence in solid tumors and metastases have been reported for decades, the influence of eosinophils on metastatic tumor growth in the lungs is unclear. We used transgenic mouse models characterized by elevated pulmonary eosinophils (IL5Tg mice) and eosinophil-deficiency (ΔdblGATA mice), as well as antibody-mediated depletion of eosinophils, to study the role of eosinophils in EO771 mammary tumor growth in the lungs. We found that IL5Tg mice exhibit reduced pulmonary metastatic colonization and decreased metastatic tumor burden compared to wild-type (WT) mice or eosinophil-deficient mice. Eosinophils co-cultured with tumor cells ex vivo produced peroxidase activity and induced tumor cell death, indicating that eosinophils are capable of releasing eosinophil peroxidase (EPX) and killing EO771 tumor cells. We found that lung eosinophils expressed phenotypic markers of activation during EO771 tumor growth in the lungs, and that metastatic growth was accelerated in eosinophil-deficient mice and in WT mice after immunological depletion of eosinophils. Our results highlight an important role for eosinophils in restricting mammary tumor cell growth in the lungs and support further work to determine whether strategies to trigger local eosinophil degranulation may decrease pulmonary metastatic growth.

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 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 categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.480
Threshold uncertainty score0.591

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 integrity0.0000.000
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 head0.013
GPT teacher head0.274
Teacher spread0.261 · 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 teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
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

Citations16
Published2022
Admission routes2
Has abstractyes

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