info:eu-repo/semantics/baccalaureateDissertation Jovanović, Marina, 1991- 142 lista 4996159 bytes Jovanović, Ivan, 1977- Arsenijević, Nebojša, 1958- Radosavljević, Gordana, 1976- Jovanović, Milan, 1963- 2021 Sinergistički efekat blokade IL-33/ST2 i PDL/PD-1 osovina na progresiju mišjeg karcinoma dojke https://phaidrakg.kg.ac.rs/o:1504 cobiss:62048009 thesis:8553 srp http://creativecommons.org/licenses/by-nc-nd/3.0/at/legalcode Iako je dobro poznato da pojedinačna blokada bilo PDL/PD-1 bilo IL-33/ST2 osovinedoprinosi efikasnijem anti-tumorskom odgovoru, simulantana blokada ovih osovinanije još uvek izučena. Indukovali smo karcinom dojke (4T1) ili karcinom kolona(ST26) BALB/c ili BALB/c ST2 nokaut miševima, a potom su dobijali anti PD-1 ilianti IL-33 antitelo Simultana blokada IL33/ST2 i PDL/PD1 je odložila pojavupalpabilnog tumora i usporila rast tumora. Naši rezultati takođe ukazuju pojačanucitotoksičnost NK ćelija prema 4T1 tumorskim ćelijama kod ST2 nokaut miševa koji sutretirani anti-PD-1 anitelom. Kod ST2 nokaut miševa koji su tretirani anti-PD-1anitelom je takođe bila povećana ekspresija miRNA-150 i miRNA-155, povećanjeekspresije NFκB i STAT3, povećana ekspresija aktivacionih markera i smanjenaekspresija imunsupresivnih markera kod NK, NKT, T limoficita, u slezini i uprimarnom tumoru. Takođe, NK ćelije izolovane iz BALB/cST2 nokaut miševa koji sutretirani anti-PD-1 anitelom, imaju veči stepen proliferacije i manji stepen apoptozeu primarnom tumoru. Akumulacija imusupresivnih ćelijskih populacija mijeloidnihsupresorskih ćelija il iT regulatornih limfocita, je kod ST2 nokaut miševa koji sutretirani anti-PD-1 anitelom bila značajno manja i u slezini i uz priamrnom tumoru.Ovi rezultati pokazuj uda simultana blokada IL-33/ST2 i PDL/PD-1 osovina mnogoefikasnije usporava progresiju tumora u odnosu na pojedinačnu blokadu, otvarajućinove mogućnosti za terapijski pristum lečenju karcinoma. Although separate blockage of either IL-33/ST2 or PDL/PD-1 axes has been shown to bebeneficial in many tumors, co-blockage of IL33/ST2 and PDL/PD-1 hasn’t been studied yet.4T1 breast cancer and CT26 colon cancer were inducted in BALB/C wild type (WT) andBALB/C ST2 knockout mice, after which mice underwent anti PD1 and anti IL-33 treatment.Co-blockage of IL33/ST2 and PDL/PD1 delayed tumor appearance and slowed tumor growth.Enhanced NK cell cytotoxicity against 4T1 tumor cells in ST2 knockout anti-PD1 treated micewas associated with overexpression of miRNA-150 and miRNA-155, upregulation of NFκB andSTAT3, increased expression of activation markers and decreased expression ofimmunosuppressive markers in splenic and primary tumor derived NK cells. NK cells from ST2knockout anti-PD1 treated mice tend to proliferate more and are less prone to apoptosis.Accumulation of immunosuppressive myeloid derived suppressor cells and regulatory T cellswas significantly impaired in spleen and primary tumor of ST2 knockout anti-PD1 treated mice.Co-blockage of IL-33/ST2 and PDL/PD-1 axes impedes tumor progression more efficiently thansingle blockage of either axes, thus offering potential new approach to immunotherapy oftumors. -