Intratumoral NK cells from human renal carcinomas display an unusual phenotype and suppressed effector functions

SECCHIARI, FLORENCIA; NÚÑEZ, SOL YANEL; ZIBLAT, ANDREA; ROVEGNO, AGUSTÍN; SIERRA, JESSICA MARIEL; REGGE, MARÍA VICTORIA; FRIEDRICH, ADRIÁN; FUERTES, MERCEDES BEATRIZ; DOMAICA, CAROLINA INÉS; ZWIRNER, NORBERTO WALTER

Mar del Plata

Congreso; 66ª Reunión Anual de la Sociedad Argentina de Inmunología; 2018

Sociedad Argentina de Inmunología

Renal cell carcinoma (RCC) is an aggressive neoplasm, characterized for being silent and asymptomatic during early stages, that becomes evident when metastasis may have already occurred. As RCC displays resistance to radio- and chemotherapy, nephrectomy constitutes the gold-standard treatment. Moreover, RCC patients exhibit a high incidence of recurrence and metastasis. To gain insight into RCC, we previously characterized the expression pattern of the ligands of the NK cell activating receptor NKG2D (NKG2DL) on peripheral blood mononuclear cells (PBMC), tumor infiltrating lymphoid cells (TIL) and tumor cells from RCC patients. Tumor cells showed high expression of MICA, while TIL, not only exhibited high expression of MICA, but also of ULBP-3 and ULBP-4. No expression was observed on PBMC from RCC patients or healthy donors (HD). Additionally, NKG2D was down-regulated on NK and CD8+ T cells in PBMC from RCC patients compared to HD, whereas tumor infiltrating NK cells (TINK) and CD8+ T cells, unexpectedly, displayed increased expression of NKG2D. To further characterize TINK, we assessed their effector functions (degranulation against K562 cells and IFN- production upon stimulation with cytokines) and compared them to peripheral blood NK cells (PBNK) from RCC patients using multicolor flow cytometry. PBNK from RCC patients displayed lower degranulation capacity and diminished IFN- production than PBNK from HD. Moreover, TINK displayed a more pronounced reduced degranulation (p