Naslov (srp)

Efekti sistemske aplikacije IL-33 na progresiju mišjeg melanoma

Autor

Jevtović, Andra, 1986-

Doprinosi

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

Opis (eng)

Melanoma is one of the most aggressive tumors, characterized by high invasiveness,metastatic potential and resistance to therapeutics. IL-33 is member of IL-1 cytokine familythat regulates both innate and acquired immune response. The role of IL-33 in tumorprogression is complex and not fully understood.The aim of the study is to evaluate effects of systemic IL-33 application on murinemelanoma progression, as well as the effects of IL-33 on modulation of antitumor immuneresponse.For the assessment of tumor growth, wild-type C57BL/6 mice were injectedsubcutaneously with B16-F1 or B16-F10 cells, whilst for experimental metastasis assays,malignant cells were injected intravenously. Using different modalities of IL-33 application,effects of the mouse recombinant IL-33 on growth and melanoma metastasis were evaluated.Effects of IL-33 on antitumor immune response in metastatic lungs were analyzed.IL-33 restricted primary tumor growth of both high metastatic (B16-F10) and lowmetastatic (B16-F1) variant, while on the opposite promoted growth of the B16-F1 melanomametastasis in the lungs. Prometastatic IL-33 activity is reflected in significant reduction ofCD8+T cells cytotoxicity and promotion of CD8+T cell immunosuppressive phenotype.There was a significant accumulation of myeloid suppressor cells and regulatory T cells in themetastatic lung. The significance of IL-33 for melanoma metastases was also documented in asignificantly increased level of serum IL-33 melanoma patients with regional metastases.These findings implicate that, despite restrictive effects on primary melanoma, IL-33promotes growth of hematogenous melanoma metastasis in mice by modulation of acquiredimmune response, thus questioning its usage in therapy of human advanced melanoma.

Opis (srp)

Melanom je jedan od najagresivnijih tumora koji karakterišu povećaninvazivni i metastatski potencijal, kao i sticanje rezistencije na terapeutike. IL-33je član familije IL-1 koji reguliše urođeni i stečeni imunski odgovor. Uloga IL-33 utumoru je kompleksna i nije u potpunosti razjašnjena.Cilj studije je da se ispitaju efekti sistemske aplikacije IL-33 na progresijumišjeg melanoma, kao i na modulaciju antitumorskog imunskog odgovora.Miševima čistog soja C57BL/6 je subkutanom aplikacijom ćelija B16-F1 iB16-F10 varijeteta mišjeg melanoma transplantiran primarni melanom, dok su imeksperimentalne metastaze indukovane posle intravenske aplikacije ćelija. Nakonrazličitih modaliteta aplikacije mišjeg rekombinantnog IL-33, ispitivan je efekatIL-33 na rast i metastaziranje melanoma. Analiziran je uticaj IL-33 na modulacijuimunskog odgovora u metastaskom tkivu pluća.IL-33 suprimira rast primarnog melanoma i sa većim (B16-F10) i sa manjimmetastatskim potencijalom (B16-F1), dok s druge strane stimuliše hematogenometastaziranje B16-F1 varijeteta melanoma u pluća. Prometastatska aktivnost IL-33 seogleda u tome što redukuje citotoksički kapacitet i favorizuje imunosupresivnifenotip CD8+T limfocita u metastatskom tkivu pluća. Zabeležena je povećanaakumulacija mijeloidnih supresorskih ćelija, kao i regulatornih T limfocita.Prometastatski efekat IL-33 dodatno je potvrđen i nalazom povećane koncentracijeIL-33 u serumu obolelih od melanoma sa detektovanim regionalnim metastazama.Dobijeni nalaz ukazuje da uprkos supresivnom delovanju na rast primarnogmelanoma, IL-33 podstiče rast hematogenih metastaza i to tako što smanjujeefikasnost stečenog antitumorskog imunskog odgovora. Prometastatski efekat IL-33 umišjem melanomu dovodi u pitanje njegovu eventualnu terapijsku primenu.

Opis (srp)

-

Jezik

srpski

Datum

2023

Licenca

Ovo delo je licencirano pod uslovima licence
Creative Commons CC BY-NC-ND 3.0 AT - Creative Commons Autorstvo - Nekomercijalno - Bez prerada 3.0 Austria License.

http://creativecommons.org/licenses/by-nc-nd/3.0/at/legalcode