PD-L1 EXPRESSION IS INDUCED ON CYTOKINE-STIMULATED HUMAN NK CELLS AND CONTRIBUTES TO IFN-γ PRODUCTION

NUÑEZ, SOL YANEL; SANTILLI, MARÍA CECILIA; FUERTES, MERCEDES BEATRIZ; SECCHIARI, FLORENCIA; FRIEDRICH, ADRIÁN DAVID; ZWIRNER, NORBERTO WALTER; SIERRA, JESSICA MARIEL; REGGE, MARÍA VICTORIA; DOMAICA, CAROLINA INÉS

San Miguel de Tucuman

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

Background: Natural Killer (NK) cells are critical effectors against tumor and virus-infected cells, and their activity is modulated by multiple inhibitory and activating receptors and cytokines. Tumor-experienced NK cells express high levels of PD-L1, and PD-L1+ NK cells inhibit T cell priming. PD-L1 cell-intrinsic signaling pathways were described in tumor cells. The objective of this work was to study PD-L1 expression on cytokine-stimulated human NK cells and to evaluate PD-L1-mediated regulation of NK cell effector functions.Methods: The expression of PD-L1 on human NK cells (CD56+ CD3- cells) from peripheral blood of healthy donors (HD) was evaluated by flow cytometry (FC). Additionally, isolated NK cells were pre-stimulated for 18 hours with IL-12+IL-15+IL-18, or IL-15+IL-18, with or without an IFN-γ-neutralizing antibody (Ab), in some experiments K562 cells were added to the cultures for the last 4 hours, in the absence or in the presence of a PD-L1 blocking Ab. PD-L1 expression, intracytoplasmic IFN-γ and degranulation (CD107a expression) were evaluated on NK cells by FC.Results: PD-L1 was expressed by a fraction of peripheral blood NK cells from all HD (24.10%± 9.55%; n=35), it was further up-regulated by IL-12+IL-15+IL-18 or IL-15+IL-18 (p