Search: WFRF:(Holmberg O) >
Fibroblast subsets ...
Fibroblast subsets in non-small cell lung cancer: Associations with survival, mutations, and immune features
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- Pellinen, T. (author)
- Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki , Helsinki, Finland
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- Paavolainen, L. (author)
- Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki , Helsinki, Finland
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- Martin-Bernabe, A. (author)
- Karolinska Institute,Karolinska Institutet
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- Araujo, R. P. (author)
- Karolinska Institute
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- Strell, Carina (author)
- Uppsala University,Uppsala universitet,Cancerimmunterapi
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- Mezheyeuski, Artur (author)
- Uppsala University,Uppsala universitet,Cancerprecisionsmedicin
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- Backman, Max, 1987- (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- La Fleur, Linnea (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Bruck, O. (author)
- Hematology Research Unit Helsinki, University of Helsinki and Comprehensive Cancer Center, Helsinki University Hospital , Helsinki, Finland,Helsinki University Central Hospital
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- Sjölund, Jonas (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Experimentell onkologi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Experimental oncology,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Holmberg, Erik, 1951 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology,Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital , Gothenburg, Sweden
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- Valimaki, K. (author)
- Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki , Helsinki, Finland
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- Brunnström, Hans (author)
- Lund University,Lunds universitet,Förbättrad diagnostik och prognostik vid lungcancer och metastaser till lunga,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Patologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Improved diagnostics and prognostics of lung cancer and metastases to the lungs,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Pathology, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Botling, Johan (author)
- Uppsala universitet,Cancerimmunterapi,Uppsala University Hospital
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- Moreno-Ruiz, P. (author)
- Karolinska Institute
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- Kallioniemi, O. (author)
- Karolinska Institutet,University of Helsinki,Science for Life Laboratory (SciLifeLab)
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- Micke, Patrick (author)
- Uppsala universitet,Cancerimmunterapi
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- Ostman, A. (author)
- Karolinska Institute,Karolinska Institutet
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(creator_code:org_t)
- 2022-09-09
- 2023
- English.
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In: Jnci-Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 115:1, s. 71-82
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Abstract
Subject headings
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- Background 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. Methods Multiplex fluorescence immunohistochemistry was employed to spatially profile the CAF landscape in 2 population-based NSCLC cohorts (n = 636) 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 (alpha SMA). The CAF subsets were analyzed for their correlations with mutations, immune characteristics, and clinical variables as well as overall survival. Results Two CAF subsets, CAF7 (PDGFRA-/PDGFRB+/FAP+/alpha SMA+) and CAF13 (PDGFRA+/PDGFRB+/FAP-/alpha SMA+), 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. Conclusions 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-based CAF profiling as a powerful tool for the discovery of clinically relevant CAF subsets.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- poor-prognosis
- expression
- immunosuppression
- heterogeneity
- impact
- fap
- Oncology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Pellinen, T.
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Paavolainen, L.
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Martin-Bernabe, ...
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Araujo, R. P.
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Strell, Carina
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Mezheyeuski, Art ...
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show more...
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Backman, Max, 19 ...
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La Fleur, Linnea
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Bruck, O.
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Sjölund, Jonas
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Holmberg, Erik, ...
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Valimaki, K.
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Brunnström, Hans
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Botling, Johan
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Moreno-Ruiz, P.
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Kallioniemi, O.
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Micke, Patrick
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Ostman, A.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Jnci-Journal of ...
- By the university
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University of Gothenburg
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Uppsala University
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Karolinska Institutet
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Lund University