In Vivo Visualizing the IFN-b Response Required for Tumor Growth Control in a Therapeutic Model of Polyadenylic-Polyuridylic Acid Administration

NOCERA, DAVID; EMILIANO ROSELLI; PAULA ARAYA; NICOLAS NUÑEZ; STEFAN LIENENKLAUS; JADWIGA JABLONSKA; SIEGFRIED WEISS; GATTI, GERARDO; MELANIE M. BRINKMANN; ANDREA KROGER; GABRIEL MORON; MARIANA MACCIONI

JOURNAL OF IMMUNOLOGY

AMER ASSOC IMMUNOLOGISTS

Lugar: Bethesda; Año: 2016 vol. 196 p. 2860 - 2869

0022-1767

The crucial role that endogenously produced IFN-b plays in eliciting animmune response against cancer has recently started to be elucidated.Endogenous IFN-b has an important role in immune surveillance and control of tumordevelopment. Accordingly, the role of TLR agonists as cancer therapeutic agentsis being revisited via the strategy of intra/peritumoral injection with theidea of stimulating the production of endogenous type I IFN inside the tumor.Polyadenylic-polyuridylic acid (poly A:U) is a dsRNA mimetic exploredempirically in cancer immunotherapy a long time ago with little knowledgeregarding its mechanisms of action. In this work, we have in vivo visualizedthe IFN-b required for the antitumor immune response elicited in a therapeuticmodel of poly A:U administration. In this study, we have identified the role ofhost type I IFNs, cell populations that are sources of IFN-b in the tumormicroenvironment, and other host requirements for tumor control in this model.One single peritumoral dose of poly A:U was sufficient to induce IFN-b, readily visualized invivo. IFN-b production relied mainly on the activation of the transcription factorIFN regulatory factor 3 and the molecule UNC93B1, indicating that TLR3 isrequired for recognizing poly A:U. CD11c+ cells were animportant, but not the only source of IFN-b. Host type I IFNsignaling was absolutely required for the reduced tumor growth, prolonged micesurvival, and the strong antitumor-specific immune response elicited upon polyA:U administration. These findingsadd newperspectives to the use of IFN-b?inducing compounds in tumor therapy.