NKG2D engagement and IFN-gamma induce the up-regulation of PD-L1 on human NK cells upon tumor recognition.

SIERRA, JESSICA MARIEL; RAFFO IRAOLAGOITÍA, XIMENA LUCÍA; ZIBLAT, ANDREA; TORRES, NICOLÁS IGNACIO; NÚÑEZ, SOL YANEL; ARAYA, ROMINA ELIZABETH; DOMAICA, CAROLINA INÉS; ZWIRNER, NORBERTO WALTER; FUERTES, MERCEDES BEATRIZ

Buenos Aires

Congreso; IV Latinamerican Society for Immunodeficiencies (LASID) Meeting, LXIII Meeting of the Argentinean Society of Immunology and II French-Argentinean Immunology Meeting.; 2015

Latinamerican Society for Immunodeficiencies (LASID) y Sociedad Argentina de Inmunología (SAI)

Background: Despite the classical function ofnatural killer (NK) cells in the elimination of tumor and virus-infected cells,novel reports show a regulatory role for NK cells in different models ofautoimmunity and viral infections. Moreover, we have recently shown that murineNK cells can control CD8+ T cell priming to tumor antigens in vivo,through regulation of DC maturation in a mechanism involving PD-1/PD-L1interactions. The objective of the present work was to study PD-L1 up-regulationin human NK cells upon tumor recognition and the underlying mechanisms. Methods: Peripheral blood mononuclear cells (PBMC) orisolated NK cells fromhealthy human donors werestimulated with IFN-g or co-cultured withK562 target tumor cells inthe presence or in the absence of anti-NKG2D or anti-IFN-g receptor blocking antibodies or using atranswell insert, andPD-L1 expression on NK cells (CD3-CD56+ cells) wasevaluated by flow cytometry. Alternatively, PBMCs were co-cultured with different cell lines (ECC-1,PC3, MDA-MB-453, CACO2, K562 and HeLa) and PD-L1 expression was analyzed on NKcells. Results: PD-L1 expression was up-regulated on NK cellsafter 48 h of stimulation with K562 cells. Transwell and NKG2D blockadeexperiments showed a dependence on direct cell-to-cell contact through NKG2Dengagement. Also, IFN-g alone was not sufficient but waspartially required to induce PD-L1 expression. Moreover, PD-L1 up-regulation onNK cells observed in response to a broader panel of human cell lines suggeststhat this constitutes a generalized phenomenon. Conclusions: Direct tumor recognition throughNKG2D induces PD-L1 up-regulation on human NK cells.