title: Melanoma cells inhibit natural killer cell function by modulating the expression of activating receptors and cytolytic activity.
abstract: Natural killer (NK) cells play a key role in tumor immune surveillance. However, adoptive immunotherapy protocols using NK cells have shown limited clinical efficacy to date, possibly due to tumor escape mechanisms that inhibit NK cell function. In this study, we analyzed the effect of coculturing melanoma cells and NK cells on their phenotype and function. We found that melanoma cells inhibited the expression of major NK receptors that trigger their immune function, including NKp30, NKp44, and NKG2D, with consequent impairment of NK cell-mediated cytolytic activity against various melanoma cell lines. This inhibitory effect was primarily mediated by indoleamine 2,3-dioxygenase (IDO) and prostaglandin E2 (PGE2). Together, our findings suggest that immunosuppressive barriers erected by tumors greatly hamper the antitumor activity of human NK cells, thereby favoring tumor outgrowth and progression.
authors.affiliation: Dipartimento di Medicina Sperimentale and Centro di Eccellenza per la Ricerca Biomedica Università degli Studi di Genova, Genova, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pietra
authors.forename: Claudia
authors.initials: C
authors.lastname: Manzini
authors.forename: Silvia
authors.initials: S
authors.lastname: Rivara
authors.forename: Massimo
authors.initials: M
authors.lastname: Vitale
authors.forename: Claudia
authors.initials: C
authors.lastname: Cantoni
authors.forename: Andrea
authors.initials: A
authors.lastname: Petretto
authors.forename: Mirna
authors.initials: M
authors.lastname: Balsamo
authors.forename: Romana
authors.initials: R
authors.lastname: Conte
authors.forename: Roberto
authors.initials: R
authors.lastname: Benelli
authors.forename: Simona
authors.initials: S
authors.lastname: Minghelli
authors.forename: Nicola
authors.initials: N
authors.lastname: Solari
authors.forename: Marina
authors.initials: M
authors.lastname: Gualco
authors.forename: Paola
authors.initials: P
authors.lastname: Queirolo
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Mingari
mesh_terms: D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D015232:Dinoprostone / Q000096:biosynthesis; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008545:Melanoma / Q000201:enzymology / Q000276:immunology*; D055607:Receptors, Natural Killer Cell / Q000276:immunology; D012878:Skin Neoplasms / Q000201:enzymology / Q000276:immunology*; D019139:Tumor Escape
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D055607:Receptors, Natural Killer Cell; D007371:Interferon-gamma; D015232:Dinoprostone