title: NK cells from malignant pleural effusions are not anergic but produce cytokines and display strong antitumor activity on short-term IL-2 activation.
abstract: NK cells are a major component of innate immunity and exert a potent antitumor 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-γ and TNF-α 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.
authors.affiliation: Department of Experimental Medicine and Center of Excellence for Biomedical Research, University of Genova, Genova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Vacca
authors.forename: Stefania
authors.initials: S
authors.lastname: Martini
authors.forename: Valentina
authors.initials: V
authors.lastname: Garelli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Passalacqua
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Mingari
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D019002:CD56 Antigen / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D052118:Lysosomal-Associated Membrane Protein 1 / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology / Q000378:metabolism; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000276:immunology / Q000378:metabolism; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000276:immunology / Q000378:metabolism; D016066:Pleural Effusion, Malignant / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D019002:CD56 Antigen; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; C527085:KLRK1 protein, human; D008024:Ligands; D052118:Lysosomal-Associated Membrane Protein 1; C522918:NCAM1 protein, human; C112260:NCR1 protein, human; C431710:NCR3 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D055627:Natural Cytotoxicity Triggering Receptor 1; D055628:Natural Cytotoxicity Triggering Receptor 3; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma