{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["8(1)"],"submitter":["Lee SY"],"pubmed_abstract":["Resistance to immune checkpoint blockade (ICB) remains a major challenge in lung adenocarcinoma (LUAD), with stromal mechanisms underlying CD8⁺ T cell exhaustion still poorly understood. By integrating single-cell, bulk, and spatial transcriptomic datasets using EcoTyper, we identified a distinct immunosuppressive ecotype, EC10, enriched for TGF-β signaling and epithelial-mesenchymal transition. EC10 exhibited spatial co-localization of fibroblasts, malignant epithelial cells, and exhausted CD8<sup>+</sup> T cells, and was consistently associated with immune exclusion, poor progression-free survival, and elevated TIDE scores across four ICB-treated LUAD cohorts. Cell-cell communication analyses revealed a dominant TGFB1-SERPINE1 signaling axis originating from fibroblasts, linking stromal remodeling to T cell dysfunction. In contrast, EC12 represented an inflamed, ICB-responsive state enriched in interferon signaling. These findings define EC10 as a spatially organized, fibroblast-driven immunosuppressive ecosystem predictive of ICB resistance, and highlight the therapeutic potential of targeting the TGF-β axis in LUAD."],"journal":["Communications biology"],"pagination":["1730"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12669596"],"repository":["biostudies-literature"],"pubmed_title":["Fibroblast TGF-β signaling defines spatial tumor ecosystems linked to immune checkpoint blockade resistance."],"pmcid":["PMC12669596"],"pubmed_authors":["Lee SY","Lee Y"],"additional_accession":[]},"is_claimable":false,"name":"Fibroblast TGF-β signaling defines spatial tumor ecosystems linked to immune checkpoint blockade resistance.","description":"Resistance to immune checkpoint blockade (ICB) remains a major challenge in lung adenocarcinoma (LUAD), with stromal mechanisms underlying CD8⁺ T cell exhaustion still poorly understood. By integrating single-cell, bulk, and spatial transcriptomic datasets using EcoTyper, we identified a distinct immunosuppressive ecotype, EC10, enriched for TGF-β signaling and epithelial-mesenchymal transition. EC10 exhibited spatial co-localization of fibroblasts, malignant epithelial cells, and exhausted CD8<sup>+</sup> T cells, and was consistently associated with immune exclusion, poor progression-free survival, and elevated TIDE scores across four ICB-treated LUAD cohorts. Cell-cell communication analyses revealed a dominant TGFB1-SERPINE1 signaling axis originating from fibroblasts, linking stromal remodeling to T cell dysfunction. In contrast, EC12 represented an inflamed, ICB-responsive state enriched in interferon signaling. These findings define EC10 as a spatially organized, fibroblast-driven immunosuppressive ecosystem predictive of ICB resistance, and highlight the therapeutic potential of targeting the TGF-β axis in LUAD.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-06-05T21:50:16.583Z","creation":"2026-05-22T03:15:17.762Z"},"accession":"S-EPMC12669596","cross_references":{"pubmed":["41326697"],"doi":["10.1038/s42003-025-09087-4"]}}