Host type I IFN signals are required for the antitumor immune response elicited by the therapeutically administered TLR3 ligand Poly AU

DAVID ANDRÉS NOCERA; NICOLAS NUÑEZ; GERARDO GATTI; ROSELLI EMILIANO; PAULA ARAYA; MARIANA MACCIONI

Los Cocos, Córdoba, Argentina

Congreso; Congreso Anual de la Sociedad Argentina de Inmunologia; 2013

Sociedad Argentina de Inmunologia

: The use of viral double-stranded RNA (dsRNA) mimetics in cancer immunotherapy has been explored for several decades with the idea of enhancing innate and adaptive immune responses and altering the tumor microenvironment. Polyadenylic?polyuridylic acid (pAU) is a synthetic analog of viral dsRNA recognized mainly by Toll like receptor 3 (TLR3) capable of triggering type I IFN production. The main goal of this work was to analyze the effect of intratumorally (i.t.) administered pAU on the specific immune response against tumor antigens in mice lacking the IFNAR1 subunit of the type I IFN receptor (IFNAR1 -/- ). Material and Methods: B16 murine melanoma cells expressing Ovalbumin (OVA) were inoculated s.c. in wild-type and IFNAR1 - / - mice. When tumors reached a measurable size (~day 12 p.i), a group of mice from each strain was i.t. treated with 50 µg of pAU (n=10, 4 doses every two days). Results: pAU-treated wild-type mice showed a significantly reduced tumor growth as well as a longer survival compared to controls (p