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dc.contributor.authorPaulsen, Erna-Elise
dc.contributor.authorKilvær, Thomas Karsten
dc.contributor.authorRakaee, Mehrdad
dc.contributor.authorRichardsen, Elin
dc.contributor.authorHald, Sigurd
dc.contributor.authorAndersen, Sigve
dc.contributor.authorBusund, Lill-Tove
dc.contributor.authorBremnes, Roy M.
dc.contributor.authorDønnem, Tom
dc.date.accessioned2018-08-01T08:50:52Z
dc.date.available2018-08-01T08:50:52Z
dc.date.issued2017-07-13
dc.description.abstractThe immune checkpoint receptor CTLA-4 plays a crucial part in negatively regulating T cell activation and maintaining self-tolerance. It is frequently overexpressed in a variety of malignancies, yet its prognostic impact in non-small cell lung cancer (NSCLC) remains unclear. We constructed tissue microarrays from tumor tissue samples and evaluated the immunohistochemical expression of CTLA-4 in 536 patients with primary resected stage I–IIIA NSCLC. Expression of CTLA-4 was analyzed in tumor and stromal primary tumor tissue and in locoregional metastatic lymph nodes. CTLA-4 expression in neither tumor epithelial cells (T-CTLA-4) nor stromal cells (S-CTLA-4) of primary tumors was significantly associated with disease-specific survival (DSS) in all patients. However, high S-CTLA-4 expression independently predicted significantly improved DSS in the squamous cell carcinoma subgroup (HR 0.62, 95% CI 0.41–0.93, P = 0.021). In contrast, there was an independent negative prognostic impact of T-CTLA-4 expression in metastatic lymph nodes (HR 1.65, 95% CI 1.03–2.65, P = 0.039). Our results indicate that the expression of CTLA-4 has diverging prognostic impacts in metastatic NSCLC lymph nodes versus primary tumors. The presented results highlight important differences in the tumor microenvironments of primary and metastatic NSCLC tissues, and have potential to guide treatment and clinical sampling strategies.en_US
dc.description.sponsorshipThe Norwegian Cancer Society The Northern Norway Health Region Authority Helse Nord RHFen_US
dc.descriptionSource at <a href=https://doi.org/10.1007/s00262-017-2039-2> https://doi.org/10.1007/s00262-017-2039-2</a>.en_US
dc.identifier.citationPaulsen, E.-E., Kilvær, T.K., Rakaee, M., Richardsen, E., Hald, S., Andersen, S., ... Dønnem, T. (2017). CTLA-4 expression in the non-small cell lung cancer patient tumor microenvironment: diverging prognostic impact in primary tumors and lymph node metastases. Cancer Immunology and Immunotherapy, 66, 1449-1461. https://doi.org/10.1007/s00262-017-2039-2en_US
dc.identifier.cristinIDFRIDAID 1501696
dc.identifier.doi10.1007/s00262-017-2039-2
dc.identifier.issn0340-7004
dc.identifier.issn1432-0851
dc.identifier.urihttps://hdl.handle.net/10037/13322
dc.language.isoengen_US
dc.publisherSpringer Verlag (Germany)en_US
dc.relation.journalCancer Immunology and Immunotherapy
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.subjectCTLA-4en_US
dc.subjectPrognosticen_US
dc.subjectNon-small cell lung canceren_US
dc.subjectImmune checkpointsen_US
dc.subjectImmunoscoreen_US
dc.titleCTLA-4 expression in the non-small cell lung cancer patient tumor microenvironment: diverging prognostic impact in primary tumors and lymph node metastasesen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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