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

Author

Listed:
  • Saskia Hartner

    (McGill University
    McGill University)

  • Hanie Abolfathi

    (Université Laval
    Institut universitaire de cardiologie et de pneumologie de Québec – Université Laval)

  • Morteza Rezanejad

    (McGill University)

  • Bridget Liu

    (McGill University)

  • Elham Karimi

    (McGill University)

  • Dakota Rogers

    (McGill University)

  • Mark Sorin

    (McGill University
    McGill University)

  • Samuel Doré

    (McGill University
    McGill University)

  • Lysanne Desharnais

    (McGill University
    McGill University)

  • Michèle Orain

    (Institut universitaire de cardiologie et de pneumologie de Québec – Université Laval)

  • William Enlow

    (Institut universitaire de cardiologie et de pneumologie de Québec – Université Laval)

  • Andréanne Gagné

    (Institut universitaire de cardiologie et de pneumologie de Québec – Université Laval
    Université Laval)

  • Yuhong Wei

    (McGill University)

  • Yohan Bossé

    (Institut universitaire de cardiologie et de pneumologie de Québec – Université Laval)

  • Daniela F. Quail

    (McGill University
    McGill University
    McGill University)

  • Philippe Joubert

    (Institut universitaire de cardiologie et de pneumologie de Québec – Université Laval
    Université Laval)

  • Logan A. Walsh

    (McGill University
    McGill University)

Abstract

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.

Suggested Citation

  • Saskia Hartner & Hanie Abolfathi & Morteza Rezanejad & Bridget Liu & Elham Karimi & Dakota Rogers & Mark Sorin & Samuel Doré & Lysanne Desharnais & Michèle Orain & William Enlow & Andréanne Gagné & Yu, 2025. "Oncogenic driver mutations underlie the spatial tumour immune landscape of non-small cell lung cancer," Nature Communications, Nature, vol. 16(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63465-4
    DOI: 10.1038/s41467-025-63465-4
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    References listed on IDEAS

    as
    1. Mark Sorin & Morteza Rezanejad & Elham Karimi & Benoit Fiset & Lysanne Desharnais & Lucas J. M. Perus & Simon Milette & Miranda W. Yu & Sarah M. Maritan & Samuel Doré & Émilie Pichette & William Enlow, 2023. "Single-cell spatial landscapes of the lung tumour immune microenvironment," Nature, Nature, vol. 614(7948), pages 548-554, February.
    2. Elham Karimi & Miranda W. Yu & Sarah M. Maritan & Lucas J. M. Perus & Morteza Rezanejad & Mark Sorin & Matthew Dankner & Parvaneh Fallah & Samuel Doré & Dongmei Zuo & Benoit Fiset & Daan J. Kloosterma, 2023. "Single-cell spatial immune landscapes of primary and metastatic brain tumours," Nature, Nature, vol. 614(7948), pages 555-563, February.
    3. Sebastijan Hobor & Maise Al Bakir & Crispin T. Hiley & Marcin Skrzypski & Alexander M. Frankell & Bjorn Bakker & Thomas B. K. Watkins & Aleksandra Markovets & Jonathan R. Dry & Andrew P. Brown & Jaspe, 2024. "Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
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