Anti-PD-1 terapija aktivira tumoricidna svojstva NKT ćelija i doprinosi ukupnom usporavanјu progresije tumora u modelu mišjeg karcinoma dojke
Sažetak
Uvod/Cilj. Imunoterapija je danas dobro poznat terapijski pristup u lečenju malignih bolesti koji se temelji na stimulisanju stečenog imunskog odgovora. Međutim, ćelije urođenog imuskog odgovora, kao što su prirodne T ćelije ubice – naturall killer T cells (NKT), takođe mogu biti bitne za uspešnu terapiju i započinjanje antitumorskog imunskog odgovora delovanjem na protein 1 programirane ćelijske smrti (PD-1). Cilj rada bio je da se ispita uticaj anti-PD-1 terapije na antitumorski imunski odgovor. Metode. Za indukciju tumora korišćene su 4T1 ćelije, singene za BALB/c miševe, nakon čega su miševi tretirani anti-PD-1 antitelom. Nakon žrtvovanja miševa, NKT ćelije, dendritske ćelije (DC) i makrofagi iz slezine i primarnog tumora analizirani su uz pomoć protočne citometrije. Rezultati. Anti-PD-1 terapija je povećala ekspresiju aktivirajućih molekula CD69, NKp46, i NKG2D u NKT ćelijama slezine i tumora. Ova terapija aktivira NKT ćelije direktno i indirektno, preko DC. Aktivirane NKT ćelije nakon anti-PD-1 terapije stiču tumoricidna svojstva direktno, preko povećanog stvaranja perforina, i indirektno, putem polarizacije makrofaga u pravcu M1 fenotipa. Zaključak. Anti-PD-1 terapija je podstakla promene fenotipa DC i makrofaga u primarnom tumorskom tkivu u pravcu antitumorske aktivnosti. Kako anti-PD-1 terapija indukuje značajne promene u NKT ćelijama, DC i makrofagima, efikasnost sveukupnog antitumorskog odgovora je veća i značajno je usporila rast tumora.
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