Characterization of Natural Killer cells from patients affected by pleural effusions. Caratterizzazione di cellule Natural Killer in pazienti affetti da versamento pleurico.

Natural killer (NK) cells are large innate lymphocytes involved in tumor recognition and eradication. NK cell activity is impaired in cancer patients and in NSCLC these cells showed a pro-angiogenic phenotype and function. We investigated whether NK cells infiltrating inflammatory or malignant pleural effusions caused by primary or metastatic tumors of different origins (iPE, ptPE and tmPE, respectively) are able to acquire pro-tumor and pro-angiogenic features. PE-NK cells are enriched in CD56bright CD16- NK cells expressing the decidual NK marker CD49a and the activation marker CD69, in addition to a lower expression of the CD57 maturation marker. Furthermore, NK cells derived from tmPE display pro-angiogenic properties: they are predominantly VEGF+ and they are able to induce capillary-like structures in vitro on human endothelial cells. Moreover, NK cells from all patient samples showed lower cytotoxicity against K562 tumor target cells and lower positivity for perforin in comparison to peripheral blood of healthy donors (hPB) NK cells. After 3-day of NK culture with IL-2, PE-NK cells restored their cytotoxicity, whereas in PB-NK cells from patients did not reach a high level of killing capacity. 3-day culture using IL-2 plus TGFβ or IL-2 added with enriched pleural effusion milieu, only partially restored the cytotoxic potential. Purified hPB NK cells treated for 7 days with IL-15 and pleural effusions acquired a pro-angiogenic phenotype, showing cell polarization towards the CD56bright CD16dim IFNγlow NK cell subset, suggesting that in the PE milieu, diverse soluble factors are able to skew cytotoxic NK cells into pro-tumor, pro-angiogenic NK cells.