Poly I:C treatment of tumors cells promote the secretion of soluble factors that improve the differentiation of APCs with a better allostimulatory function

GERARDO GATTI; DAVID ANDRÉS NOCERA; EMILIANO ROSELLI; PAULA ARAYA; CONSTANCIO GIRAUDO

Los Cocos

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA. LOS COCOS, NOVIEMBRE 2013.; 2013

SAI

Monocytes (Mo) attracted by tumor-induced chronic inflammation differentiate to antigen presenting cells (APCs), the type of which depends on cues in the local tumor milieu. Polyinosine?polycytidylic acid (poly I:C) is a synthetic analog of viral dsRNA and a strong inducer of type I interferon (IFN). We have previously shown that a human lung cancer cell line (A549) responds to poly I:C stimulation, producing IFN-β at levels that are capable of improving the activation status of human Mo-derived dendritic cells (DCs). In this work we attempted to see if conditioned media obtained from non- stimulated (CM) or poly I:C-stimulated tumor cells (PIC-CM) are capable of altering the normal differentiation of Mo to immature DCs. When the differentiation was done in the presence of CM, differentiated APCs displayed a downregulated HLA-DR expression (MFI:640) compared to those differentiated in the presence of medium alone (MFI:791). In contrast, these levels increased when PIC-CM was present (MFI: 791). Then, we evaluated the allogeneic stimulatory capacity of differentiated APCs in a mixed leucocyte reaction. When APCs were differentiated in the presence of PIC-CM, significantly increased levels of IFN-γ was observed compared to controls (528±47 vs 365±6 pg/ml, p