Phagocytosis of tumor cells by monocytes trigger IL-18 secretion which contributes to PD-L1 upregulation on NK cells

SIERRA, JESSICA MARIEL; TROTTA, ALDANA; REGGE, MARÍA VICTORIA; FRIEDRICH, ADRIÁN D.; GANTOV, MARIANA; SANTILLI, MARÍA CECILIA; NÚÑEZ, SOL YANEL; SECCHIARI, FLORENCIA; DOMAICA, CAROLINA INÉS; ZWIRNER, NORBERTO WALTER; FUERTES, MERCEDES BEATRIZ

Buenos Aires

Congreso; 69ª Reunión Anual de la Sociedad Argentina de Inmunología; 2021

Sociedad Argentina de Inmunología

NK cells are key effectors against tumor and virus-infected cells. However, evidence of a regulatory role during autoimmunity and viral infections is emerging. We have identified a subset of immunoregulatory, PD-L1-expressing tumor-infiltrating NK cells in tumor-bearing mice and in patients with renal cell carcinoma (RCC). In vitro, PD-L1 expression was induced on NK cells from healthy donors (HD) upon tumor cell recognition through NKG2D and was further up-regulated by monocyte (Mo)-derived IL-18. To additionally explore this circuit, the aim of this work was to characterize the underlying mechanisms that control IL-18 production by Mo. To this end, peripheral blood mononuclear cells (PBMC) from HD were cultured with K562 cells in the absence or in the presence of different pharmacological inhibitors of pathways that could lead to IL-18 production. While an ATP receptor antagonist (A740003) or inhibitors of ROS (catalase), NOS (L-NAME), or autophagy (Bafilomycin) had no effect, the inhibition of phagocytosis using cytochalasin D abolished IL-18 secretion (assessed by ELISA, p