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Record W4414514026 · doi:10.1038/s41467-025-63465-4

Oncogenic driver mutations underlie the spatial tumour immune landscape of non-small cell lung cancer

2025· article· en· W4414514026 on OpenAlexafffund
Saskia Hartner, Hanie Abolfathi, Morteza Rezanejad, Bridget Liu, Elham Karimi, Dakota Rogers, Mark Sorin, Samuel Doré, Lysanne Desharnais, Michèle Orain, William Enlow, Andréanne Gagné, Yuhong Wei, Yohan Bossé, Daniela F. Quail, Philippe Joubert, Logan A. Walsh

Bibliographic record

VenueNature Communications · 2025
Typearticle
Languageen
FieldMedicine
TopicCancer Immunotherapy and Biomarkers
Canadian institutionsMcGill Genome CentreUniversité LavalInstitut universitaire de cardiologie et de pneumologie de QuébecMcGill UniversityMcGill University Health Centre
FundersCanadian Institutes of Health ResearchInstitut universitaire de cardiologie et de pneumologie de Québec, Université LavalFonds de Recherche du Québec - SantéQuébec Consortium for Drug DiscoveryMcGill University
KeywordsKRASLung cancerMutationImmune systemAdenocarcinomaTumor microenvironmentCancerTumour heterogeneityGene

Abstract

fetched live from OpenAlex

Lung adenocarcinoma (LUAD) is a molecularly diverse form of lung cancer characterized by distinct oncogenic driver mutations that influence both tumour biology and clinical outcomes. Understanding the interplay between these oncogenic drivers and the tumour microenvironment (TME) is crucial for improving therapeutic strategies and patient management. Here, we investigate the impact of driver mutations on the composition and spatial architecture of the TME in LUAD. Using imaging mass cytometry (IMC), we analyse tumour samples from 157 LUAD patients, integrating genomic and clinical data to link specific mutations with tumour characteristics. Unique patterns are associated with mutated KRAS and EGFR tumours with TP53 co-mutations, suggesting these co-mutations reshape the TME and promote resistance to tyrosine kinase inhibitors (TKIs). Overall, our findings highlight the complex interplay between oncogenic driver mutations and the TME in LUAD, underscoring the importance of integrating genomic and cellular data to understand the underlying tumour behaviour and prognosis. Oncogenic driver mutations can influence the tumour biology of lung adenocarcinomas. Here, authors analyse 157 LUAD samples using imaging mass cytometry to reveal how these mutations impact the tumour microenvironment and clinical outcomes.

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)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
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 head0.012
GPT teacher head0.309
Teacher spread0.298 · 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 designObservational
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

Citations6
Published2025
Admission routes2
Has abstractyes

Explore more

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