NCRs and DNAM-1 mediate NK cell recognition and lysis of human and mouse melanoma cell lines in vitro and in vivo.
NK cells use a variety of receptors to detect abnormal cells, including tumors and their metastases. However, in the case of melanoma, it remains to be determined what specific molecular interactions are involved and whether NK cells control metastatic progression and/or the route of dissemination. Here we show that human melanoma cell lines derived from LN metastases express ligands for natural cytotoxicity receptors (NCRs) and DNAX accessory molecule-1 (DNAM-1), two emerging NK cell receptors key for cancer cell recognition, but not NK group 2 member D (NKG2D). Compared with cell lines derived from metastases taken from other anatomical sites, LN metastases were more susceptible to NK cell lysis and preferentially targeted by adoptively transferred NK cells in a xenogeneic model of cell therapy. In mice, DNAM-1 and NCR ligands were also found on spontaneous melanomas and melanoma cell lines. Interference with DNAM-1 and NCRs by antibody blockade or genetic disruption reduced killing of melanoma cells. Taken together, these results show that DNAM-1 and NCRs are critical for NK cell-mediated innate immunity to melanoma cells and provide a background to design NK cell-based immunotherapeutic strategies against melanoma and possibly other tumors.
Lakshmikanth
Tadepally
T
Department of Experimental and Clinical Medicine, University of Catanzaro "Magna Graecia", Italy.
Burke
Shannon
S
Ali
Talib Hassan
TH
Kimpfler
Silvia
S
Ursini
Francesco
F
Ruggeri
Loredana
L
Capanni
Marusca
M
Umansky
Viktor
V
Paschen
Annette
A
Sucker
Antje
A
Pende
Daniela
D
Groh
Veronika
V
Biassoni
Roberto
R
Höglund
Petter
P
Kato
Masashi
M
Shibuya
Kazuko
K
Schadendorf
Dirk
D
Anichini
Andrea
A
Ferrone
Soldano
S
Velardi
Andrea
A
Kärre
Klas
K
Shibuya
Akira
A
Carbone
Ennio
E
Colucci
Francesco
F
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D008024:Ligands; D008207:Lymphatic Metastasis / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000235:genetics / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000276:immunology; D055636:Receptors, Natural Cytotoxicity Triggering / Q000276:immunology / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D000098862:T Lineage-Specific Activation Antigen 1
D000906:Antibodies; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D000098862:T Lineage-Specific Activation Antigen 1; D004268:DNA-Binding Proteins; D053631:Interleukin Receptor Common gamma Subunit; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D055627:Natural Cytotoxicity Triggering Receptor 1; C118384:Ncr1 protein, mouse; C499308:Rag2 protein, mouse; D055636:Receptors, Natural Cytotoxicity Triggering