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

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 Kadang, Roni Rayes, Philippe Joubert, Sophie Camilleri-Broët, Pierre-Olivier Fiset, Daniela F. Quail, Jonathan D. Spicer () and Logan A. Walsh ()
Additional contact information
Lysanne Desharnais: McGill University
Mark Sorin: McGill University
Morteza Rezanejad: McGill University
Bridget Liu: McGill University
Elham Karimi: McGill University
Aline Atallah: McGill University
Anikka M. Swaby: McGill University
Miranda W. Yu: McGill University
Samuel Doré: McGill University
Saskia Hartner: 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
Jonathan D. Spicer: McGill University
Logan A. Walsh: McGill University

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-56546-x

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