Title (srp)

Sinergistički efekat blokade IL-33/ST2 i PDL/PD-1 osovina na progresiju mišjeg karcinoma dojke

Author

Jovanović, Marina, 1991-

Contributor

Jovanović, Ivan, 1977-
Arsenijević, Nebojša, 1958-
Radosavljević, Gordana, 1976-
Jovanović, Milan, 1963-

Description (srp)

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.

Description (srp)

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Description (eng)

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.

Object languages

Serbian

Date

2021

Rights

Creative Commons License
This work is licensed under a
CC BY-NC-ND 3.0 AT - Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Austria License.

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