IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Monocyte-derived IL-18 enhance PD-L1 expression on tumor-experienced human NK cells
Autor/es:
JESSICA MARIEL SIERRA; ANDREA ZIBLAT; CAROLINA INES DOMAICA; JESSICA MARIEL SIERRA; ANDREA ZIBLAT; CAROLINA INES DOMAICA; FLORENCIA SECCHIARI; ADRIAN FRIEDRICH; MERCEDES BEATRIZ FUERTES; FLORENCIA SECCHIARI; ADRIAN FRIEDRICH; MERCEDES BEATRIZ FUERTES; SOL YANEL NUÑEZ; MARIA VICTORIA REGGE; NORBERTO WALTER ZWIRNER; SOL YANEL NUÑEZ; MARIA VICTORIA REGGE; NORBERTO WALTER ZWIRNER
Lugar:
Mar del Plata
Reunión:
Congreso; LXVI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2018
Institución organizadora:
Sociedad Argentina de Investigaciones Clinicas y Sociedad Argentina de Inmunologia
Resumen:
Natural killer (NK) cells play an important role in the elimination of tumor and virus-infected cells, however, recently evidence of a regulatory role is emerging in different models of autoimmunity, transplants and viral infections. In the tumor context, we have demonstrated that NK cells from tumor bearing mice showed an up-regulated expression of the inhibitory molecule PD-L1 and restrict CD8+ T cell priming. Moreover, in human NK cells, direct tumor recognition through NKG2D receptor induced the expression of PD-L1, which was further up-regulated in the presence of peripheral blood mononuclear cells (PBMCs) through IL-18. However, the underlying mechanisms that control these interactions are unknown. Thus, the aim of this work was to identify the IL-18-producing cell population and the signals and cells involved in its induction, which results in PD-L1 expression on human NK cells. To distinguish between NK cell-derived factors versus tumor cell-derived factors, we generated conditioned medium (CM) from NK cells cultured with K562 tumor cells and CM from serum-deprived apoptotic K562 cells. Then, PBMCs were stimulated with these CM or with K562 cells in the absence or in the presence of an IFN-g neutralizing antibody. K562 cells and both CM induced IL-18 secretion by PBMCs, measured by ELISA, which was partially reduced by IFN-g blockade. Next, to identify the IL-18-producing population, we cultured NK cells with K562 cells, with or without syngeneic monocytes. The addition of monocytes resulted in a higher IL-18 secretion evaluated by ELISA (p