{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:17:50Z","timestamp":1791598670735,"version":"4.3.4"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002794","name":"Swedish Cancer Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Lions Cancer Foundation Uppsala"},{"DOI":"10.13039\/100016669","name":"Sj\u00f6berg Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016669","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sweden, the Instrumentarium Science Foundation"},{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9lius Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010711","name":"Cancer Foundation Finland","doi-asserted-by":"publisher","award":["190116"],"award-info":[{"award-number":["190116"]}],"id":[{"id":"10.13039\/501100010711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010711","name":"Cancer Foundation Finland","doi-asserted-by":"publisher","award":["61-6200"],"award-info":[{"award-number":["61-6200"]}],"id":[{"id":"10.13039\/501100010711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["333050"],"award-info":[{"award-number":["333050"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["340273"],"award-info":[{"award-number":["340273"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["337036"],"award-info":[{"award-number":["337036"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Cancer-associated fibroblasts (CAFs) are molecularly heterogeneous mesenchymal cells that interact with malignant cells and immune cells and confer anti- and protumorigenic functions. Prior in situ profiling studies of human CAFs have largely relied on scoring single markers, thus presenting a limited view of their molecular complexity. Our objective was to study the complex spatial tumor microenvironment of non-small cell lung cancer (NSCLC) with multiple CAF biomarkers, identify novel CAF subsets, and explore their associations with patient outcome.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Multiplex fluorescence immunohistochemistry was employed to spatially profile the CAF landscape in 2 population-based NSCLC cohorts (n\u2009=\u2009636) using antibodies against 4 fibroblast markers: platelet-derived growth factor receptor-alpha (PDGFRA) and -beta (PDGFRB), fibroblast activation protein (FAP), and alpha-smooth muscle actin (\u03b1SMA). The CAF subsets were analyzed for their correlations with mutations, immune characteristics, and clinical variables as well as overall survival.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Two CAF subsets, CAF7 (PDGFRA-\/PDGFRB+\/FAP+\/\u03b1SMA+) and CAF13 (PDGFRA+\/PDGFRB+\/FAP-\/\u03b1SMA+), showed statistically significant but opposite associations with tumor histology, driver mutations (tumor protein p53 [TP53] and epidermal growth factor receptor [EGFR]), immune features (programmed death-ligand 1 and CD163), and prognosis. In patients with early stage tumors (pathological tumor-node-metastasis IA-IB), CAF7 and CAF13 acted as independent prognostic factors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Multimarker-defined CAF subsets were identified through high-content spatial profiling. The robust associations of CAFs with driver mutations, immune features, and outcome suggest CAFs as essential factors in NSCLC progression and warrant further studies to explore their potential as biomarkers or therapeutic targets. This study also highlights multiplex fluorescence immunohistochemistry\u2013based CAF profiling as a powerful tool for the discovery of clinically relevant CAF subsets.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jnci\/djac178","type":"journal-article","created":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T20:41:50Z","timestamp":1662669710000},"page":"71-82","source":"Crossref","is-referenced-by-count":68,"title":["Fibroblast subsets in non-small cell lung cancer: Associations with survival, mutations, and immune features"],"prefix":"10.1093","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9652-7373","authenticated-orcid":false,"given":"Teijo","family":"Pellinen","sequence":"first","affiliation":[{"name":"Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki , Helsinki, 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Uppsala University , Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artur","family":"Mezheyeuski","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Uppsala University , Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Backman","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Uppsala University , Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linnea","family":"La Fleur","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Uppsala University , Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Br\u00fcck","sequence":"additional","affiliation":[{"name":"Hematology Research Unit Helsinki, University of Helsinki and Comprehensive Cancer Center, Helsinki University Hospital , Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Sj\u00f6lund","sequence":"additional","affiliation":[{"name":"Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University Cancer Centre, Lund University , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5107-4550","authenticated-orcid":false,"given":"Erik","family":"Holmberg","sequence":"additional","affiliation":[{"name":"Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital , Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"V\u00e4lim\u00e4ki","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki , Helsinki, 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