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dc.contributor.authorYang, Nannan
dc.contributor.authorLode, Kristin
dc.contributor.authorBerzaghi, Rodrigo
dc.contributor.authorIslam, Md Ashraful
dc.contributor.authorMartinez, Inigo Zubiavrre
dc.contributor.authorHellevik, Turid
dc.date.accessioned2021-11-19T08:29:03Z
dc.date.available2021-11-19T08:29:03Z
dc.date.issued2021-01-22
dc.description.abstractRecent studies have demonstrated that radiotherapy is able to induce anti-tumor immune responses in addition to mediating direct cytotoxic effects. Cancer-associated fibroblasts (CAFs) are central constituents of the tumor stroma and participate actively in tumor immunoregulation. However, the capacity of CAFs to influence immune responses in the context of radiotherapy is still poorly understood. This study was undertaken to determine whether ionizing radiation alters the CAF-mediated immunoregulatory effects on natural killer (NK) cells. CAFs were isolated from freshly resected non-small cell lung cancer tissues, while NK cells were prepared from peripheral blood of healthy donors. Functional assays to study NK cell immune activation included proliferation rates, expression of cell surface markers, secretion of immunomodulators, cytotoxic assays, as well as production of intracellular activation markers such as perforin and granzyme B. Our data show that CAFs inhibit NK cell activation by reducing their proliferation rates, the cytotoxic capacity, the extent of degranulation, and the surface expression of stimulatory receptors, while concomitantly enhancing surface expression of inhibitory receptors. Radiation delivered as single high-dose or in fractioned regimens did not reverse the immunosuppressive features exerted by CAFs over NK cells in vitro, despite triggering enhanced surface expression of several checkpoint ligands on irradiated CAFs. In summary, CAFs mediate noticeable immune inhibitory effects on cytokine-activated NK cells during co-culture in a donor-independent manner. However, ionizing radiation does not interfere with the CAF-mediated immunosuppressive effects.en_US
dc.identifier.citationYang N, Lode K, Berzaghi RB, Islam A, Martinez IZ, Hellevik T. Irradiated tumor fibroblasts avoid immune recognition and retain immunosuppressive functions over natural killer cells. Frontiers in Immunology. 2021;11:602530en_US
dc.identifier.cristinIDFRIDAID 1947422
dc.identifier.doi10.3389/fimmu.2020.602530
dc.identifier.issn1664-3224
dc.identifier.urihttps://hdl.handle.net/10037/23074
dc.language.isoengen_US
dc.publisherFrontiers Mediaen_US
dc.relation.ispartofLode, K. (2023). Cancer associated fibroblasts and their regulatory functions in the context of radiotherapy. (Doctoral thesis). <a href=https://hdl.handle.net/10037/29913>https://hdl.handle.net/10037/29913</a>.
dc.relation.journalFrontiers in Immunology
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2021 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801en_US
dc.subjectVDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801en_US
dc.titleIrradiated tumor fibroblasts avoid immune recognition and retain immunosuppressive functions over natural killer cellsen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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