Oncogenic driver mutations underlie the spatial tumour immune landscape of non-small cell lung cancer
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.
Authors
- Daniela F. Quail (ORCID: https://orcid.org/0000-0002-6969-3250)
- Andréanne Gagné (ORCID: https://orcid.org/0000-0002-3833-4159)
- Saskia Hartner
- Samuel Doré (ORCID: https://orcid.org/0009-0007-7503-3316)
- Hanie Abolfathi
- Yuhong Wei (ORCID: https://orcid.org/0000-0002-5333-5547)
- Elham Karimi (ORCID: https://orcid.org/0000-0002-2204-0789)
- William Enlow
- Michèle Orain (ORCID: https://orcid.org/0000-0002-9779-1851)
- Mark Sorin (ORCID: https://orcid.org/0000-0002-0341-217X)
- Yohan Bossé (ORCID: https://orcid.org/0000-0002-3067-3711)
- Lysanne Desharnais
- Dakota Rogers (ORCID: https://orcid.org/0000-0001-5574-3088)
- Logan A. Walsh (ORCID: https://orcid.org/0000-0001-8771-2577)
- Morteza Rezanejad (ORCID: https://orcid.org/0000-0001-8744-8534)
- Philippe Joubert (ORCID: https://orcid.org/0000-0001-7784-6387)
- Bridget Liu
Institutions
- McGill University Health Centre (CA)
- McGill Genome Centre (CA)
- Institut universitaire de cardiologie et de pneumologie de Québec (CA)
- Université Laval (CA)
- McGill University (CA)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-09-25
- DOI
- https://doi.org/10.1038/s41467-025-63465-4
- Citations
- 2
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 2.09
Funders
- McGill University
- Québec Consortium for Drug Discovery
- Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval
- Canadian Institutes of Health Research
- Fonds de Recherche du Québec - Santé