Natural killer (NK) cells are effector lymphocytes crucial in tumor recognition and eradication. However, NK cell activity is often impaired in cancer patients and in NSCLC we recently demonstrated that they acquire proangiogenic phenotype and function. Here we characterized NK cells from peripheral blood (PB) and pleural effusion (PE) of patients with inflammatory diseases or with primary (mesothelioma) or metastatic tumors (including melanoma, lung, breast, hepatocellular, renal and neuroendocrine carcinoma). The highest percentage of PE CD56brightCD16- NK cell subset is found in malignant (60%), then in primary tumor (40%) and finally in inflammatory conditions (35%). Interestingly, PE-NK cells from tumor patients display increased expression of the decidual marker CD49a, together with enhancement of the activatory surface antigen CD69 and decreased levels of the CD57 maturation marker. Although all NK cells from PE display higher expression of VEGF in comparison to autologous and healthy PB NK cells, only metastatic PE-NK cells were statistically different. The cytotoxic potential was impaired, as all PE NK cells showed lower perforin content as compared to autologous and healthy PB NK cells. PE-NK cells efficiently responded to IL-2 stimulation in vitro, however addition of TGF or metastatic PE-cell-free supernatants in the culture strongly impaired NK cell cytotoxicity. These data suggest a relevant role for PE tumor microenvironment in shaping NK cell polarization and establishing an alternative NK cell activation status.
Pleural effusion NK cells from metastatic tumors display pro-angiogenic features and pleural effusion fluids block their response to IL-2 treatment
ZANELLATO, SILVIA;BASSANI, BARBARA;Bosi, A.;CATTONI, MARIA ANGELA;SAMPIETRO, CHIARA;IMPERATORI, ANDREA SELENITO;DOMINIONI, LORENZO;BRUNO, ANTONINO;MORTARA, LORENZO;NOONAN, DOUGLAS
2017-01-01
Abstract
Natural killer (NK) cells are effector lymphocytes crucial in tumor recognition and eradication. However, NK cell activity is often impaired in cancer patients and in NSCLC we recently demonstrated that they acquire proangiogenic phenotype and function. Here we characterized NK cells from peripheral blood (PB) and pleural effusion (PE) of patients with inflammatory diseases or with primary (mesothelioma) or metastatic tumors (including melanoma, lung, breast, hepatocellular, renal and neuroendocrine carcinoma). The highest percentage of PE CD56brightCD16- NK cell subset is found in malignant (60%), then in primary tumor (40%) and finally in inflammatory conditions (35%). Interestingly, PE-NK cells from tumor patients display increased expression of the decidual marker CD49a, together with enhancement of the activatory surface antigen CD69 and decreased levels of the CD57 maturation marker. Although all NK cells from PE display higher expression of VEGF in comparison to autologous and healthy PB NK cells, only metastatic PE-NK cells were statistically different. The cytotoxic potential was impaired, as all PE NK cells showed lower perforin content as compared to autologous and healthy PB NK cells. PE-NK cells efficiently responded to IL-2 stimulation in vitro, however addition of TGF or metastatic PE-cell-free supernatants in the culture strongly impaired NK cell cytotoxicity. These data suggest a relevant role for PE tumor microenvironment in shaping NK cell polarization and establishing an alternative NK cell activation status.
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