TYPE I IFNs DETERMINE EXOSOME COMPOSITION FROM PANCREATIC TUMOR CELLS MODIFYING THE NK CELLS ACTIVITY

ESTEFANÍA S. PAPARATTO; ELIDA ALVAREZ; MARIA NOÉ GARCIA; DANIEL GRASSO; DANIELA L. PAPADEMETRIO; NADIA PAGLILLA

Tucumán

Congreso; LXVII Reunión Científica Anual de la Sociedad Argentina de Inmunología; 2019

Sociedad Argentina de Inmunología

Pancreatic ductal adenocarcinoma (PDAC) induces immunotolerance where exosomes act as intercellular messengers, carrying molecules from tumor to immune cells. Type-I IFNs have antitumoral properties in a model-dependent behavior. We investigated the role of IFNα2a and IFNβ in tumor-derived exosomes composition and their impact on Natural Killer cells (NK) activity.Exosomes were collected from supernatants of MIAPaCa-2 PDAC cell line (EXOM-Basal), treated with IFNα2b (EXOM-IFNα2b) or IFNβ (EXOM-IFNβ) at 2, 6 or 24h. NK cells from Buffy-Coats of healthy donors (Ethical statement CEIC-Res#677-19) were purified by magnetic MAbs negative selection. NK cytotoxicity was evaluated by CFSE/PI stain on K562 cells. We incubated NK cells with EXOM-Basal, EXOM-IFNα2b or EXOM-IFNβ during 2h. CFSE dyed-K562 cells were added in ratio 5:1 (NK:K562) for 4h. IFNγ release was evaluated in supernatants of cytotoxicity assays by ELISA. CD107a expression was evaluated in co-cultures of NK:K562 ratio 1:1. 2 and 6h EXOM-IFNα2b decreased NK cytotoxicity (34%, 49%, respectively p