Tumor-experienced NK cells inhibit T cell proliferation and activation through PD-L1

SIERRA, JESSICA M.; RAFFO IRAOLAGOITIA, XIMENA L.; SECCHIARI, FLORENCIA; ZIBLAT A; NUÑEZ, SOL Y.; TORRES, NICOLAS; REGGE, MARÍA VICTORIA; DOMAICA CI; ZWIRNER NW; FUERTES MB

Congreso; AACR Annual Meeting; 2018

Classical functions of Natural Killer (NK) cells include the elimination of tumor and virus-infected cells, however, novel reports show a regulatory role for NK cells in different models of autoimmunity and viral infections. Our previous results demonstrated that NK cells from tumor bearing mice express the inhibitory molecule PD-L1 and control the magnitude of CD8+ T cell priming to tumor antigens in vivo. Moreover, we also observed that PD-L1 expression is up-regulated on human NK cells upon tumor recognition, but little is known about the function of human PD-L1hi NK cells. Thus, the objective of this work was to further study the phenotype and activity of tumor-experienced human PD-L1hi NK cells and their possible immunoregulatory role. To this end, we cultured peripheral blood mononuclear cells (PBMC) from healthy human donors with K562 tumor cells for 48 h and we evaluated the expression of the activation markers CD25 and CD69, and the effector molecules TRAIL, FasL, CD107a and IFN-γ on PD-L1hi and PD-L1-/low NK cells (CD56+CD3-) by flow cytometry. We observed that all markers were preferentially expressed in PD-L1hi NK cells (p