Cancer-associated fibroblast phenotypes are associated with patient outcome in non-small cell lung cancer

• DOI: 10.1016/j.ccell.2023.12.021
• Publication Date: 2024-01-18T15:33:43Z
• Authors: Lena Cords; Stefanie Engler; Martina Haberecker; Jan Hendrik Rüschoff; Holger Moch; Natalie de Souza; Bernd Bodenmiller
• Keywords: Lung Neoplasms; Spatial analysis; 610 Medicine & health; Fibroblasts; Prognosis; Article; Imaging mass cytometry; Phenotype; Cancer-Associated Fibroblasts; Non-small cell lung cancer; 10049 Institute of Pathology and Molecular Pathology; Carcinoma, Non-Small-Cell Lung; Tumor Microenvironment; Humans; Single cell; Cancer-associated fibroblasts; Imaging mass cytometry; Single cell; Spatial analysis; Non-small cell lung cancer; 11493 Department of Quantitative Biomedicine; Cancer-associated fibroblasts

ISSN:1878-3686<br/>Despite advances in treatment, lung cancer survival rates remain low. A better understanding of the cellular heterogeneity and interplay of cancer-associated fibroblasts (CAFs) within the tumor microenvironment will support the development of personalized therapies. We report a spatially resolved single-cell imaging mass cytometry (IMC) analysis of CAFs in a non-small cell lung cancer cohort of 1,070 patients. We identify four prognostic patient groups based on 11 CAF phenotypes with distinct spatial distributions and show that CAFs are independent prognostic factors for patient survival. The presence of tumor-like CAFs is strongly correlated with poor prognosis. In contrast, inflammatory CAFs and interferon-response CAFs are associated with inflamed tumor microenvironments and higher patient survival. High density of matrix CAFs is correlated with low immune infiltration and is negatively correlated with patient survival. In summary, our data identify phenotypic and spatial features of CAFs that are associated with patient outcome in NSCLC.<br/>Cancer Cell, 42 (3)<br/>ISSN:1535-6108<br/>