Desharnais Lysanne, Sorin Mark, Rezanejad Morteza, Liu Bridget, Karimi Elham, Atallah Aline, Swaby Anikka M, Yu Miranda W, Doré Samuel, Hartner Saskia, Fiset Benoit, Wei Yuhong, Kadang Baharak, Rayes Roni, Joubert Philippe, Camilleri-Broët Sophie, Fiset Pierre-Olivier, Quail Daniela F, Spicer Jonathan D, Walsh Logan A
Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC, Canada.
Department of Human Genetics, McGill University, Montreal, QC, Canada.
Nat Commun. 2025 Feb 4;16(1):1345. doi: 10.1038/s41467-025-56546-x.
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.
肺癌是癌症相关死亡的主要原因。对这些肿瘤内免疫微环境的深入了解可能会促进更精确、高效的治疗，尤其是免疫靶向治疗。肺腺癌（LUAD）和肺鳞状细胞癌（LUSC）之间的空间结构差异相对未被充分探索。在此，我们将成像质谱流式细胞术应用于一组年龄、性别和吸烟史等临床因素匹配的LUAD和LUSC患者队列，以分析102例非小细胞肺癌（NSCLC）患者的204张肿瘤组织病理学图像。通过分析相互作用和更广泛的细胞网络，我们对肿瘤微环境进行探究，以了解免疫细胞在临床匹配的腺癌和鳞状细胞癌亚组中是如何在空间上组织的。这种空间分析揭示了免疫细胞聚集的独特模式，特别是在巨噬细胞群体中，这在腺癌和鳞状细胞癌中与患者预后的相关性不同，提示了潜在的治疗干预新策略。我们的研究结果强调了在研究空间免疫格局时分别分析NSCLC组织学亚型的重要性，因为微环境特征和细胞相互作用因亚型而异。认识到这些差异对于设计针对每种亚型独特免疫结构的精准治疗至关重要，最终可改善患者预后。
