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Record W4413974852 · doi:10.1101/2025.09.04.674147

γδ T cells modulate anti-tumor immunity in small cell lung cancer

2025· preprint· en· W4413974852 on OpenAlexaff
Jin Ng, Yue You, Jonas B. Hess, Sarah A. Best, Alex Caneborg, Marcel Schmiel, Dale I. Godfrey, Yin Wu, Richard W. Tothill, Casey J. A. Anttila, Tracey M. Baldwin, Shalin H. Naik, Ariena Kersbergen, Tracy L. Leong, Julie George, Matthew E. Ritchie, Nicholas A. Gherardin, Hui‐Fern Koay, Peter F. Hickey, Daniel Steinfort

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldMedicine
TopicLung Cancer Research Studies
Canadian institutionsInstitute of Infection and Immunity
FundersInstitut National Du CancerNational Health and Medical Research CouncilState Government of VictoriaBundesministerium für Bildung und ForschungCancer Council VictoriaDeutsche ForschungsgemeinschaftAustralian GovernmentMarshfield Clinic Research FoundationWellcome TrustInternational Association for the Study of Lung Cancer
KeywordsImmunityLung cancerCancer researchTumor cellsCell mediated immunityMedicineImmunologyImmune systemOncology

Abstract

fetched live from OpenAlex

SUMMARY Small cell lung cancer (SCLC) is a highly aggressive neoplasm with limited sensitivity to anti-PD-(L)1 blockade, likely due to the epigenetic silencing of MHC-I. Elucidating MHC-I-independent immune recognition mechanisms is therefore crucial for enhancing treatment responses and improving clinical outcomes in a greater number of patients. Leveraging single cell approaches, we discovered γδ T cell infiltration in biospecimens from patients with SCLC. Despite PD-1 expression, γδ T cells maintained a cytotoxic transcriptional profile, suggestive of an anti-tumor role. Indeed, high γδ T cell infiltration predicted improved response to anti-PD-L1 immunotherapy in patients with SCLC. Moreover, using pre-clinical models, we demonstrated that γδ T cells are effective at tarlatamab (DLL3-CD3 BiTE) redirected SCLC killing and that zoledronate, an FDA-approved compound, can sensitize SCLC cells to γδ T cell-mediated killing. Thus, our findings suggest that engaged γδ T cells are potentially valuable targets for SCLC therapy.

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 score0.002
Threshold uncertainty score0.007

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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.018
GPT teacher head0.282
Teacher spread0.265 · 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

Citations2
Published2025
Admission routes1
Has abstractyes

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Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicLung Cancer Research StudiesFrench-language works237,207