TNFΑ BLOCKADE INCREASES SURVIVAL OF MICE DISPLAYING PREMALIGNANT LESIONS INDUCED BY TTP ABLATION AND K-RAS ACTIVATION IN THE TONGUE

DARÍO FERRI; MARINA AYRE; ARIZA BARREÑO AMARANTA; SANCHEZ V; URTREGER ALEJANDRO; PAPARELLA ML; KORDON EDITH; ANA RAIMONDI

Mar del Plata

Congreso; Reunión Anual SAIC 2022; 2022

SAIC

Squamous cell carcinoma of the head and neck (HNSCC) is thesixth most common cancer worldwide, being tongue SCC the mostcommon malignancy found in the oral cavity. Tristetraprolin (TTP)is a RNA binding protein that binds to target mRNA and destabilizesit, reducing protein expression. TTP has the ability to regulateproinflammatory mediators such as TNFα and IL6 that promotetumorigenesis. Previously, we have characterized a mouse modelwhere TTP is ablated in the oral cavity (TTP KO: K14-CreERTAM/TTPflox/flox). These mice developed mild dysplastic lesions in the tongueover time along with inflammatory infiltrate in the connective tissue(mast cells and CD11b cells). Besides, we analyzed the status ofthe NFkB pathway and we found increased levels of p65 and p-p65.Furthermore, we generated K14-CreERtam/TTP-/-/K-rasG12D+/- animals(compound mice) that exhibited a complete oral phenotype and presenteda significant reduction in survival time. Here, to asses themechanism underlying the development of the mentioned lesionstogether with the inflammatory infiltrate we tested the role of TNFαin this model. We treated TTP KO and compound mice with a TNFαdecoy receptor (Etanercept: 0.01mg/g of body weight, 3 times aweek during 2 months and 2-3 weeks respectively). Etanercepttreatment reduced 37% mast cells infiltration in TTP-KO mice vsuntreated control group (TB+/mm2, p