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dc.contributor.advisorMartinez, Inigo Zubiavrre
dc.contributor.authorAkhtar, Muhammad Asad
dc.date.accessioned2019-02-15T11:06:46Z
dc.date.available2019-02-15T11:06:46Z
dc.date.issued2018-11-19
dc.description.abstractSummary Background/aim of the study: Carcinoma-associated fibroblasts (CAFs) represents a heterogeneous population of cells and are considered one of the dominant stromal component of solid tumours, performing a crucial role in tumour proliferation and metastasis. The main objective of this study was to investigate the immunoregulatory features of CAFs isolated from non-small cell lung carcinomas on macrophages and the potential effects of ionizing radiation on observed effects. Methods: The study comprise primary cultures of CAFs isolated from freshly resected NSCLC (Non Small Lung Cancer) tumours (n=8) and monocyte-derived macrophages prepared from peripheral blood of healthy donors. The experimental settings included both co-cultures and incubations of macrophages with CAF-conditioned medium. Moreover, CAF-mediated effects were studied in both uncommitted and M1-polarized macrophages. Functional assays to study macrophage polarisation included expression of cell surface markers by flow cytometry, production of nitric oxide by flow cytometry and secretion of inflammatory cytokines by ELISA. Results: All functional assays illustrated that CAFs both in co-culture and by conditioned medium, promote changes on uncommitted macrophages (M0) that harmonize with both M1 and M2 phenotypes. CAFs, both in co-culture and by conditioned medium, could inhibit some of the pro-inflammatory features of M1 macrophages as demonstrated by strong inhibition of nitric oxide production, strong inhibition of proinflammatory cytokines secretion and a reduction of some M1 surface markers. Importantly, radiation given at high dose (1x18 Gy) or in fractioned regimens (3x6 Gy) is not able to modify substantially the immunoregulatory features exerted by CAFs over macrophages in vitro. Last, protein expression analyses in CAF supernatants show that both irradiated and non-irradiated CAFs produced approximately the same levels of cytokines. Conclusion: This study display that CAFs-derived soluble factors mediate measurable changes on uncomitted macrophages (M0) and down-regulate pro-inflammatory features of M1 polarized macrophages, even though the soluble factors accountable for this shift remains unknown. On the other hand, this study also illustrates that low dose fractioned radiotherapy and single high dose radiotherapy do not curtail the immunosuppressive effect of CAFs.en_US
dc.identifier.urihttps://hdl.handle.net/10037/14697
dc.language.isoengen_US
dc.publisherUiT Norges arktiske universiteten_US
dc.publisherUiT The Arctic University of Norwayen_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2018 The Author(s)
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/3.0en_US
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0)en_US
dc.subject.courseIDMBI-3911
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750en_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750en_US
dc.title“EFFECT OF IRRADIATION ON THE IMMUNOREGULATORY FUNCTIONS EXERTED BY TUMOUR FIBROBLASTS ON MACROPHAGES”en_US
dc.typeMaster thesisen_US
dc.typeMastergradsoppgaveen_US


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Attribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0)
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