(1) Ziblat A (2) Iraolagoitia XLR (3) Nu–ez SY (4) Torres NI (5) Secchiari F (6) Sierra JM (7) Spallanzani RG (8) Rovegno A (9) Secin FP (10) Fuertes MB (11) Domaica CI (12) Zwirner NW

Frontiers in immunology | Free PMC Article

Although natural killer (NK) cells infiltrate clear cell renal cell carcinomas (ccRCC), the most frequent malignancy of the kidney, tumor progression suggests that they become dysfunctional. As ccRCC-driven subversion of NK cell effector functions is usually accompanied by phenotypic changes, analysis of such alterations might lead to the identification of novel biomarkers and/or targets in immuno-oncology. Consequently, we performed a phenotypic analysis of peripheral blood NK cells (PBNK) and tumor-infiltrating NK cells (TINK) from ccRCC patients. Compared to HD, PBNK from ccRCC patients exhibited features of activated cells as shown by CD25, CD69 and CD62L expression. They also displayed increased expression of DNAM-1, CD48, CD45, MHC-I, reduced expression of NKG2D, and higher frequencies of CD85j(+) and PD-1(+) cells. In addition, compared to PBNK from ccRCC patients, TINK exhibited higher expression of activation markers, tissue residency features and decreased expression of the activating receptors DNAM-1, NKp30, NKp46, NKp80 and CD16, suggesting a more inhibitory phenotype. Analysis of The Cancer Genome Atlas (TCGA) revealed that CD48, CD45, CD85j and PD-1 are significantly overexpressed in ccRCC and that their expression is associated with an NK cell infiltration signature. Calculation of z-scores revealed that their expression on PBNK, alone or combined, distinguished ccRCC patients from HD. Therefore, these molecules emerge as novel potential biomarkers and our results suggest that they might constitute possible targets for immunotherapy in ccRCC patients.

Author Info: (1) Laboratorio de Fisiopatolog’a de la Inmunidad Innata, Instituto de Biolog’a y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina. (2) Laboratorio de Fisiopatolog’a

Author Info: (1) Laboratorio de Fisiopatolog’a de la Inmunidad Innata, Instituto de Biolog’a y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina. (2) Laboratorio de Fisiopatolog’a de la Inmunidad Innata, Instituto de Biolog’a y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina. (3) Laboratorio de Fisiopatolog’a de la Inmunidad Innata, Instituto de Biolog’a y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina. (4) Laboratorio de Fisiopatolog’a de la Inmunidad Innata, Instituto de Biolog’a y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina. (5) Laboratorio de Fisiopatolog’a de la Inmunidad Innata, Instituto de Biolog’a y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina. (6) Laboratorio de Fisiopatolog’a de la Inmunidad Innata, Instituto de Biolog’a y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina. (7) Laboratorio de Fisiopatolog’a de la Inmunidad Innata, Instituto de Biolog’a y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina. (8) Centro de Educaci—n MŽdica e Investigaciones Cl’nicas "Norberto Quirno" (CEMIC), Servicio de Urolog’a, Buenos Aires, Argentina. (9) Centro de Educaci—n MŽdica e Investigaciones Cl’nicas "Norberto Quirno" (CEMIC), Servicio de Urolog’a, Buenos Aires, Argentina. (10) Laboratorio de Fisiopatolog’a de la Inmunidad Innata, Instituto de Biolog’a y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina. (11) Laboratorio de Fisiopatolog’a de la Inmunidad Innata, Instituto de Biolog’a y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina. (12) Laboratorio de Fisiopatolog’a de la Inmunidad Innata, Instituto de Biolog’a y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina. Departamento de Qu’mica Biol—gica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.

Citation: Front Immunol 2021 12:681615 Epub06/04/2021

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/34149719

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