UP-REGULATED EXPRESSION OF PD-L1 ON CYTOKINE-ACTIVATED NK CELLS INVOLVES JNK, p38 MAPK and NF-κB PATHWAYS.

MARIANA GANTOV; JESSICA MARIEL SIERRA; ADRIÁN DAVID FRIEDRICH; MARÍA SOFÍA AMARILLA; DANIELA GONZALEZ PIÑERO; MARÍA VICTORIA REGGE; ALDANA TROTTA; MARÍA CECILIA SANTILLI; MARÍA NATALIA RUBINSZTAIN ; BELÉN CANDELA LOZADA MONTANARI; CAROLINA INÉS DOMAICA; NORBERTO WALTER ZWIRNER; MERCEDES BEATRIZ FUERTES

Congreso; Reunion anual de la SAI; 2023

Natural Killer (NK) cells are key effectors in the antitumoral and antiviral immuneresponse. However, these cells can also adopt a regulatory role, suppressing T cellresponses. We have shown that tumor-experienced human and mouse NK cellsexpress high levels of PD-L1 and are able to inhibit CD8+ T cell priming.Immunosuppressive PD-L1+ NK cells can also emerge upon viral infections or aftercytokine stimulation. The aim of this work was to study the mechanisms and signalingpathways involved in PD-L1 up-regulation in human NK cells in proinflammatoryconditions. To this end, human NK cells from healthy donors were isolated andstimulated with the proinflammatory cytokines IL-12, IL-15 and IL-18 individually or incombination. After 24 hours PD-L1 expression and intracellular IFN-γ were evaluatedby flow cytometry. We observed that when added individually, none of the cytokinesincreased PD-L1 expression or IFN-γ production in NK cells. However, thecombination of IL-12+IL-18 significantly increased the frequency of PD-L1 expressingNK cells (p