Soluble factors released by DU145 human prostate cancer cells stimulated with Poly I:C-liposomes promote the activation of monocyte-derived dendritic cells.

GERARDO GATTI, CONSTANCIO GIRAUDO, MARIANA MACCIONI

Buenos Aires

Congreso; FIRST FRENCH-ARGENTINE IMMUNOLOGY CONGRESS. FAIC 2010; 2010

Sociedad Argentina Inmunologia

Tumors derived factors significantly inhibit the generation as well as the activation of dendritic cells (DCs). Polyinosinic-polycytidylic acid (Poly I:C, PIC), a dsRNA analog, can trigger the secretion of type I Interferon and induce apoptosis in tumor cells via the innate recognition receptors melanoma-differentiationassociated gene (MDA)-5 and retinod-inducible gene (RIG)-I in the cytosol or via Toll-like receptors 3 in intracellular endosomes. Thus, we hypothesized that prostate tumor cells activated via these receptors could release soluble factors that can restore the suppressive effect of tumor derived factors on DCs. In order to see if factors secreted by PIC-stimulated DU145 cells could somehow overcome this already described inhibitory effect, DU145 cells were cultured with PIC-liposome complex (0.1 ƒÊg/ml) for 4 hours, washed three times with PBS, incubated for 20 additional hours and the culture supernatant was then harvested and filtered (CM-PIC). As control, non stimulated DU145 cell culture supernatant was also collected (CM). Human monocyte- derived DCs (MoDCs) cells were matured with LPS in the presence of CM-PIC or CM. MoDCs stimulated with LPS in presence of CM-PIC increased the expression costimulatory molecules compared to MoDC stimulated with LPS in presence of CM (CD86 MFI: 178 vs 97; CD80 MFI: 35 vs 26; CD40, MFI: 23 vs 14). Furthermore, the levels of IL12p70 were significantly increased in LPS-stimulated MoCDs incubated with CM-PIC at 24h (670.1E}2.9 vs 90.3E}16.3 pg/ml), and at 48h (926.5E}14.2 vs 127.5E}1.5 pg/ml), p<0.05. MoDCs stimulated only with PIC (0.1 ƒÊg/ml) did not show any sign of maturation. Together, our results provide new insights in the use of PIC-liposomes as therapeutic agents to enhance the antitumoral immune response.