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Spatially mapping the tumour immune microenvironments of non-small cell lung cancer

Author

Listed:
  • Lysanne Desharnais

    (McGill University
    McGill University)

  • Mark Sorin

    (McGill University
    McGill University)

  • Morteza Rezanejad

    (McGill University)

  • Bridget Liu

    (McGill University)

  • Elham Karimi

    (McGill University)

  • Aline Atallah

    (McGill University
    McGill University)

  • Anikka M. Swaby

    (McGill University
    McGill University)

  • Miranda W. Yu

    (McGill University
    McGill University)

  • Samuel Doré

    (McGill University
    McGill University)

  • Saskia Hartner

    (McGill University
    McGill University)

  • Benoit Fiset

    (McGill University)

  • Yuhong Wei

    (McGill University)

  • Baharak Kadang

    (McGill University)

  • Roni Rayes

    (McGill University)

  • Philippe Joubert

    (Laval University)

  • Sophie Camilleri-Broët

    (McGill University)

  • Pierre-Olivier Fiset

    (McGill University)

  • Daniela F. Quail

    (McGill University
    McGill University
    McGill University)

  • Jonathan D. Spicer

    (McGill University
    McGill University Health Center)

  • Logan A. Walsh

    (McGill University
    McGill University)

Abstract

Lung cancer is the leading cause of cancer-related deaths. An enhanced understanding of the immune microenvironments within these tumours may foster more precise and efficient treatment, particularly for immune-targeted therapies. The spatial architectural differences between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are relatively unexplored. Here, we applied imaging mass cytometry to a balanced cohort of LUAD and LUSC patients, matched for clinical factors such as age, sex, and smoking history, to analyze 204 histopathology images of tumours from 102 individuals with non-small cell lung cancer (NSCLC). By analyzing interactions and broader cellular networks, we interrogate the tumour microenvironment to understand how immune cells are spatially organized in clinically matched adenocarcinoma and squamous cell carcinoma subsets. This spatial analysis revealed distinct patterns of immune cell aggregation, particularly among macrophage populations, that correlated with patient prognosis differentially in adenocarcinoma and squamous cell carcinoma, suggesting potential new strategies for therapeutic intervention. Our findings underscore the importance of analyzing NSCLC histological subtypes separately when investigating the spatial immune landscape, as microenvironmental characteristics and cellular interactions differed by subtype. Recognizing these distinctions is essential for designing precision therapies tailored to each subtype’s unique immune architecture, ultimately enhancing patient outcomes.

Suggested Citation

  • Lysanne Desharnais & Mark Sorin & Morteza Rezanejad & Bridget Liu & Elham Karimi & Aline Atallah & Anikka M. Swaby & Miranda W. Yu & Samuel Doré & Saskia Hartner & Benoit Fiset & Yuhong Wei & Baharak , 2025. "Spatially mapping the tumour immune microenvironments of non-small cell lung cancer," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56546-x
    DOI: 10.1038/s41467-025-56546-x
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    References listed on IDEAS

    as
    1. Hartland W. Jackson & Jana R. Fischer & Vito R. T. Zanotelli & H. Raza Ali & Robert Mechera & Savas D. Soysal & Holger Moch & Simone Muenst & Zsuzsanna Varga & Walter P. Weber & Bernd Bodenmiller, 2020. "The single-cell pathology landscape of breast cancer," Nature, Nature, vol. 578(7796), pages 615-620, February.
    2. Julia Kargl & Stephanie E. Busch & Grace H. Y. Yang & Kyoung-Hee Kim & Mark L. Hanke & Heather E. Metz & Jesse J. Hubbard & Sylvia M. Lee & David K. Madtes & Martin W. McIntosh & A. McGarry Houghton, 2017. "Neutrophils dominate the immune cell composition in non-small cell lung cancer," Nature Communications, Nature, vol. 8(1), pages 1-11, April.
    3. 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.
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