ULOGA TNF-α I IFN-γ U INTERAKCIJAMA TUMORSKIH STANICA I STANICA TUMORSKOG MIKROOKOLIŠA U PRIMARNOM MEDIJASTINALNOM B-STANIČNOM LIMFOMU

doctoral thesis

• Title (english): THE ROLE OF TNF-α AND IFN-γ IN THE INTERACTIONS BETWEEN TUMOUR CELLS AND TUMOUR MICROENVIRONMENT CELLS IN PRIMARY MEDIASTINAL B CELL LYMPHOMA
• Author: Paula Gršković
• Mentor: Petra Korać (mentor)
• Committee member: Inga Urlić (predsjednik povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2024-05-28, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 577 - Biochemistry. Molecular biology. Biophysics

Abstract

Primarni medijastinalni B-stanični limfom (PMBCL) je agresivni tip nehodgkinskog limfoma (NHL). Dijeli karakteristike s difuznim B-velikostaničnim limfomom (DLBCL), ali i s klasičnim Hodgkinovim limfomom (cHL), uključujući aberacije gena uključenih u regulaciju imunosnog odgovora. U ovom istraživanju ekspresija gena TNF-α, IFN-γ, cREL, CXCL10, CXCR3, PD-L1 i PD-1 u uzorcima tkiva PMBCL-a bila je uspoređena s njihovom ekspresijom u netumorskim limfocitima B i T metodom lančane reakcije polimerazom u stvarnom vremenu (qPCR). Modelne stanične linije PMBCL-a Farage, U2940, MedB-1 i Karpas1106p bile su tretirane s različitim koncentracijama TNF-α i IFN-γ tijekom 24 i 48 sati, a zatim se kvantificirala ekspresija gena cREL, CXCL10 i PD-L1 metodom qPCR. Dulji tretman s TNF-α uzrokovao je povišenje ekspresije cREL, što bi moglo utjecati na ekspresiju nizvodnih gena. Tretman s IFN-γ potaknuo je visoku ekspresiju CXCL10, koja je potencijalno bila niska u uzorcima tumora pacijenata i netretiranim staničnim linijama zbog niske ekspresije IFN-γ. Ekspresija PD-L1 nije pokazala ujednačen odgovor na tretmane u različitim staničnim linijama. Ovi rezultati sugeriraju da tumorske stanice stvaraju upalni mikrookoliš i reguliraju kemotaksiju limfocita T kako bi izbjegle imunosni odgovor.

Abstract (english)

Primary mediastinal B-cell lymphoma (PMBCL) is an aggressive type of non-Hodgkin lymphoma (NHL). It shares features with diffuse large B-cell lymphoma (DLBCL), but also with classical Hodgkin lymphoma (cHL), including aberrations of genes involved in the regulation of immune response. In this study, the expression of genes TNF-α, IFN-γ, cREL, CXCL10, CXCR3, PD-L1 and PD-1 was compared between PMBCL tissue samples and non-tumour B- and T-cells using quantitative polymerase chain reaction (qPCR). PMBCL model cell lines Farage, U2940, MedB-1 and Karpas1106p were treated with different concentrations of TNF-α and IFN-γ over 24 and 48 hours, which was followed by the quantification of cREL, CXCL10 and PD-L1 expression using qPCR. Prolonged exposure to TNF-α increased the expression of cREL, and possibly the expression of downstream genes. IFN-γ strongly induced CXCL10 expression, which seemed to be inhibited in non-treated PMBCL cell lines and patients’ tissue samples. The expression of PD-L1 did not display uniform response to the treatments across various cell lines. These results suggest that PMBCL tumour cells create proinflammatory microenvironment and regulate T-cell chemotaxis in order to avoid immune response.

• Keywords: tumorski mikrookoliš; PMBCL; TNF-α; IFN-γ; PD-L1
• Keywords (english): tumour microenvironment; PMBCL; TNF-α; IFN-α; PD-L1
• Language: croatian
• URN:NBN: urn:nbn:hr:217:667323
• Promotion: 2024
• Study programme: Title: Doctoral study; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti u području prirodnih znanosti (doktor/doktorica znanosti u području prirodnih znanosti)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-06-04 08:58:59