title: Enrichment of CD56(dim)KIR + CD57 + highly cytotoxic NK cells in tumour-infiltrated lymph nodes of melanoma patients.
abstract: An important checkpoint in the progression of melanoma is the metastasis to lymph nodes. Here, to investigate the role of lymph node NK cells in disease progression, we analyze frequency, phenotype and functions of NK cells from tumour-infiltrated (TILN) and tumour-free ipsilateral lymph nodes (TFLN) of the same patients. We show an expansion of CD56(dim)CD57(dim)CD69 + CCR7 +KIR+ NK cells in TILN. TILN NK cells display robust cytotoxic activity against autologous melanoma cells. In the blood of metastatic melanoma patients, the frequency of NK cells expressing the receptors for CXCL8 receptor is increased compared with healthy subjects, and blood NK cells also express the receptors for CCL2 and IL-6. These factors are produced in high amount in TILN and in vitro switch the phenotype of blood NK cells from healthy donors to the phenotype associated with TILN. Our data suggest that the microenvironment of TILN generates and/or recruits a particularly effective NK cell subset.
authors.affiliation: Department of Experimental and Clinical Medicine "G. Salvatore", University of Catanzaro 'Magna Graecia', Catanzaro, 88100, Italy.|Department of Microbiology, College of Medicine, University of Thi-Qar, Nasseriah, 64001, Iraq.
authors.forename: Talib Hassan
authors.initials: TH
authors.lastname: Ali
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Baronissi Campus, Baronissi, 84081, Italy.|Department of Pharmacy, University of Salerno, Fisciano,84084, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Pisanti
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Baronissi Campus, Baronissi, 84081, Italy.|Department of Pharmacy, University of Salerno, Fisciano,84084, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Ciaglia
authors.affiliation: Human Tumors Immunobiology Unit, Department of Experimental Oncology and Molecular Medicine (R.M. and A.A.), and Melanoma and Sarcoma Unit, Department. of Surgery (M.S.), Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, 20133, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Mortarini
authors.affiliation: Human Tumors Immunobiology Unit, Department of Experimental Oncology and Molecular Medicine (R.M. and A.A.), and Melanoma and Sarcoma Unit, Department. of Surgery (M.S.), Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, 20133, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Anichini
authors.affiliation: Department of Experimental and Clinical Medicine "G. Salvatore", University of Catanzaro 'Magna Graecia', Catanzaro, 88100, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Garofalo
authors.affiliation: Department of Experimental and Clinical Medicine "G. Salvatore", University of Catanzaro 'Magna Graecia', Catanzaro, 88100, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Tallerico
authors.affiliation: Human Tumors Immunobiology Unit, Department of Experimental Oncology and Molecular Medicine (R.M. and A.A.), and Melanoma and Sarcoma Unit, Department. of Surgery (M.S.), Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, 20133, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Santinami
authors.affiliation: Department of Experimental and Clinical Medicine "G. Salvatore", University of Catanzaro 'Magna Graecia', Catanzaro, 88100, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Gulletta
authors.affiliation: Department of Experimental and Clinical Medicine "G. Salvatore", University of Catanzaro 'Magna Graecia', Catanzaro, 88100, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Ietto
authors.affiliation: Istituto di Endocrinologia e Oncologia Sperimentale, IEOS-CNR, c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, Napoli, 80131, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Galgani
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Baronissi Campus, Baronissi, 84081, Italy.|IRCCS Multimedica, Milano, 20099, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matarese
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Baronissi Campus, Baronissi, 84081, Italy.|Department of Pharmacy, University of Salerno, Fisciano,84084, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bifulco
authors.affiliation: Department of Surgery, Harvard Medical School, Boston, Massachussets, 02115, USA.
authors.forename: Soldano
authors.initials: S
authors.lastname: Ferrone
authors.affiliation: Department of Obstetrics and Gynaecology, University of Cambridge Clinical School, NIHR Cambridge Biomedical Research Centre, Cambridge,CB2 OXY, UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: Colucci
authors.affiliation: Lab. of Molecular Immunology, Department of Experimental Medicine, University of Genova, Genova, 16126, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.affiliation: Department of Microbiology Tumor and Cell Biology, Karolinska Institute, Stockholm, 171 77, Sweden.
authors.forename: Klas
authors.initials: K
authors.lastname: Kärre
authors.affiliation: Department of Experimental and Clinical Medicine "G. Salvatore", University of Catanzaro 'Magna Graecia', Catanzaro, 88100, Italy.|Department of Microbiology Tumor and Cell Biology, Karolinska Institute, Stockholm, 171 77, Sweden.
authors.forename: Ennio
authors.initials: E
authors.lastname: Carbone
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D018959:CD57 Antigens / Q000378:metabolism; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D054400:Receptors, CCR7 / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D054343:Receptors, KIR2DL2 / Q000378:metabolism; D054344:Receptors, KIR2DL3 / Q000378:metabolism; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology; D059016:Tumor Microenvironment / Q000276:immunology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D019002:CD56 Antigen; D018959:CD57 Antigens; D037181:Lectins, C-Type; D054400:Receptors, CCR7; D019947:Receptors, Interleukin-6; D054343:Receptors, KIR2DL2; D054344:Receptors, KIR2DL3; D000099192:CD69 Antigens; C515370:CCR7 protein, human; C515077:KIR2DL2 protein, human; C515078:KIR2DL3 protein, human