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dc.contributor.authorKilvær, Thomas Karsten
dc.contributor.authorRakaee, Mehrdad
dc.contributor.authorHellevik, Turid
dc.contributor.authorØstman, Arne
dc.contributor.authorStrell, Carina
dc.contributor.authorBremnes, Roy M.
dc.contributor.authorBusund, Lill-Tove
dc.contributor.authorDønnem, Tom
dc.contributor.authorMartinez, Inigo Zubiavrre
dc.date.accessioned2018-05-08T12:46:06Z
dc.date.available2018-05-08T12:46:06Z
dc.date.issued2018-02-07
dc.description.abstractObjectives: <br> Selective targeting of cancer-associated fibroblasts (CAFs) has been proposed to synergize with immune-checkpoint inhibitors. While the roles of CAFs in cancer development are well described, their immune-regulatory properties remain incompletely understood. This study investigates correlations between CAF and immune-markers in tumor stroma from nonsmall cell lung cancer (NSCLC) patients, and examines whether a combination of CAF and immune cell scores impact patient prognosis. <br>Methods: <br> Tumor specimens from 536 primary operable stage I-III NSCLC patients were organized in tissue microarrays. Expression of protein-markers was evaluated by immunohistochemistry. <br>Results: <br> Fibroblast and stromal markers PDGFRα, PDGFRβ, FAP-1 and vimentin showed weak correlations while αSMA, and Masson’s trichrome did not correlate with any of the investigated markers. Hierarchical clustering indicated the existence of different CAF-subsets. No relevant correlations were found between any CAF-marker and the immune-markers CD3, CD4, CD8, CD20, CD68, CD1a, CD56, FoxP3 and CD45RO. High density of fibroblast-activation protein positive mesenchymal cells (CAFFAP) was associated with better prognosis in tumors with high infiltration of CD8 and CD3 T-lymphocytes. <br>Conclusions: <br> The presented data suggest that CAFs, irrespective of identity, have low influence on the degree of tumor infiltration by inflammatory- and/or immune-cells. However, CAFFAP may exert immuno-adjuvant roles in NSCLC, and targeting CAFs should be cautiously considered.en_US
dc.description.sponsorshipThe Northern Norway Regional Health Authority, SPP1137-13 and SFP1138-13 The Norwegian Cancer Society, 9223 Erna & Olav Aakre Foundation for Cancer Research The publication fund of UiT The Arctic University of Norway.en_US
dc.descriptionSource at: <a href=http://doi.org/10.1371/journal.pone.0192157> http://doi.org/10.1371/journal.pone.0192157 </a>en_US
dc.identifier.citationKilvær, T. K., Rakaee, M., Hellevik, T., Østman, A., Strell, C., Bremnes, R. M., ... Martinez, I. Z. (2018). Tissue analyses reveal a potential immune-adjuvant function of FAP-1 positive fibroblasts in non-small cell lung cancer. PLoS ONE, 13:e0192157(2). http://doi.org/10.1371/journal.pone.0192157en_US
dc.identifier.cristinIDFRIDAID 1564558
dc.identifier.doi10.1371/journal.pone.0192157. eCollection 2018
dc.identifier.issn1932-6203
dc.identifier.urihttps://hdl.handle.net/10037/12712
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.journalPLoS ONE
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762en_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762en_US
dc.titleTissue analyses reveal a potential immune-adjuvant function of FAP-1 positive fibroblasts in non-small cell lung canceren_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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