European Journal of Gynaecological Oncology.. 2012 Nov 27:0. doi: 10.1002/eji.201242783. [Link]
Vacca P, Martini S, Garelli V, Passalacqua G, Moretta L, Mingari MC.
Department of Experimental Medicine and Center of Excellence for Biomedical Research, University of Genova, Genova, Italy.
NK cells are a major component of innate immunity and exert a potent anti-tumor effect both in vitro and in vivo. However, NK cells infiltrating solid tumors have been shown to display severely impaired functional capabilities. In this study we analyzed NK cells present in pleural effusions (PEs) of patients with primary or metastatic tumors of different origin, including mesothelioma and lung, breast, colon, gastric, bladder and uterus carcinoma. In all instances, freshly isolated PE-NK cells displayed a CD56(bright) phenotype and expressed normal levels of both activating receptors and HLA class I-specific inhibitory receptors. In addition, they rapidly released large amounts of IFN-Î³ and TNF-Î± after stimulation. Upon culture in IL-2, they acquired a potent cytolytic activity against both allogeneic and autologous tumor cells. Tumor cell lysis was primarily mediated by NKG2D and NKp30 and partially by NKp46 and DNAM-1, in agreement with the expression of the corresponding ligands on tumor cells. The finding that PE-NK cells are not functionally impaired and that they can efficiently kill tumor cells upon short-term IL-2 activation may offer important clues for the development of novel approaches in tumor immunotherapy.