Phenotypic characterization of NK cells in human Renal Cell Carcinoma

ZIBLAT, ANDREA; TORRES, NICOLÁS IGNACIO; RAFFO IRAOLAGOITÍA, XIMENA LUCÍA; SPALLANZANI, RAÚL GERMÁN; NÚÑEZ, SOL YANEL; SECCHIARI, FLORENCIA; SIERRA, JESSICA MARIEL; ARAYA, ROMINA ELIZABETH; SECÍN, FERNANDO; ROVEGNO, AGUSTÍN; DOMAICA, CAROLINA INÉS; FUERTES, MERCEDES BEATRIZ; ZWIRNER, NORBERTO WALTER

Mar del Plata

Congreso; 64a Reunión Anual de la Sociedad Argentina de Inmunología; 2016

Sociedad Argentina de Inmunología

Renalcell 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 andchemotherapy. Natural killer (NK) cells play a key role in tumor immunesurveillance through a cytotoxic activity and the secretion of pro-inflammatorycytokines that promote an adaptive antitumor response. Several activating andinhibitory receptors regulate NK cells effector functions. In RCC patients itwas observed a positive correlation between the percentage of tumorinfiltrating NK cells (TINKs) and a better prognosis. Moreover, the frequencyof TINKs and of NK cells in peripheral blood mononuclear cells (PBNKs)inversely correlated with tumor grade, suggesting the existence of a tumorimmunosuppressive effect on NK cells. However, the phenotype of NK cells in RCCremains unexplored. Therefore, the aim of this work was to phenotypicallycharacterize TINKs and PBNKs of RCC patients. Flow cytometry analysis revealed ahigher 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 ahigher 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 thattumor microenvironment induces TINKs with an altered phenotype that may lead toNK cells with less functional capacity. Furthermore, PBNKs phenotype of RCCpatients may compromise the immune surveillance against circulating cancercells. Besides, CD48 and CD45 expression in PBNKs may constitute diagnostic biomarkersin RCC patients.