Phenotypic characterization of NK cells in human Renal Cell Carcinoma

ZIBLAT A; TORRES NI; IRAOLAGOITIA XL; SPALLANZANI RG; NUÑEZ SY; SECCHIARI F; SIERRA JM; ARAYA RE; SECIN FP; ROVEGNO A; DOMAICA CI; FUERTES MB; ZWIRNER NW

Mar del Plata

Congreso; LXIV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2016

SAI

Renal cell carcinoma (RCC) is among the 10 most frequent cancers in the western world. Surgery is the main treatment as kidney cancers are resistant to radiation and chemotherapy. Natural killer (NK) cells play a key role in tumor immune surveillance through a cytotoxic activity and the secretion of pro-inflammatory cytokines that promote an adaptive antitumor response. Several activating and inhibitory receptors regulate NK cells effector functions. In RCC patients it was observed a positive correlation between the percentage of tumor infiltrating NK cells (TINKs) and a better prognosis. Moreover, the frequency of TINKs and of NK cells in peripheral blood mononuclear cells (PBNKs) inversely correlated with tumor grade, suggesting the existence of a tumor immunosuppressive effect on NK cells. However, the phenotype of NK cells in RCC remains unexplored. Therefore, the aim of this work was to phenotypically characterize TINKs and PBNKs of RCC patients. Flow cytometry analysis revealed a higher percentage of positive cells and/or expression of CD25, CD69, ILT2 (p0.01), DNAM-1, CD45 (p0.001) and CD48 (p0.0001), and a lower percentage of positive cells or expression of CD62L, CD56 (p0.05) and NKG2D (p0.001) in PBNKs of RCC patients in comparison with healthy donors. Also, we detected a higher percentage of positive cells and/or expression of CD56 (p0.05),CD69 (p0.0001) and PD-1 (p0.01), and a lower percentage of positive cells and/or expression of CCR7, CD57, NKG2D (p0.05), 2B4, NKp46 (p0.01), CD16, DNAM-1, NKp80 (p0.001), CD62L and NKp30 (p0.0001) on TINKs compared to PBNKs of RCC patients. Therefore, our results suggest that tumor microenvironment induces TINKs with an altered phenotype that may lead to NK cells with less functional capacity. Furthermore, PBNKs phenotype of RCC patients may compromise the immunesurveillance against circulating cancer cells. Besides, CD48 and CD45 expression in PBNKs may constitute diagnostic biomarkers in RCC patients.