NCRs and DNAM-1 mediate NK cell recognition and lysis of human and mouse melanoma cell lines in vitro and in vivo.

Abstract	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.
Authors	Tadepally Lakshmikanth, Shannon Burke, Talib Hassan Ali, Silvia Kimpfler, Francesco Ursini, Loredana Ruggeri, Marusca Capanni, Viktor Umansky, Annette Paschen, Antje Sucker, Daniela Pende, Veronika Groh, Roberto Biassoni, Petter Höglund, Masashi Kato, Kazuko Shibuya, Dirk Schadendorf, Andrea Anichini, Soldano Ferrone, Andrea Velardi, Klas Kärre, Akira Shibuya, Ennio Carbone, Francesco Colucci
Journal	The Journal of clinical investigation (J Clin Invest) Vol. 119 Issue 5 Pg. 1251-63 (May 2009) ISSN: 1558-8238 [Electronic] United States
PMID	19349689 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antibodies Antigens, Differentiation, T-Lymphocyte Antigens, Ly CD226 antigen DNA-Binding Proteins Interleukin Receptor Common gamma Subunit Ligands Lymphocyte Function-Associated Antigen-1 Natural Cytotoxicity Triggering Receptor 1 Ncr1 protein, mouse Rag2 protein, mouse Receptors, Natural Cytotoxicity Triggering
Topics	Animals Antibodies (immunology, pharmacology) Antigens, Differentiation, T-Lymphocyte (immunology, metabolism) Antigens, Ly (genetics, metabolism) Cell Line, Tumor Cytotoxicity Tests, Immunologic Cytotoxicity, Immunologic (drug effects, immunology) DNA-Binding Proteins (genetics) Humans Immunotherapy, Adoptive (methods) Interleukin Receptor Common gamma Subunit (genetics) Killer Cells, Natural (immunology, metabolism, transplantation) Ligands Lymphatic Metastasis (immunology) Lymphocyte Function-Associated Antigen-1 (metabolism) Melanoma (immunology, metabolism, pathology, therapy) Melanoma, Experimental (metabolism) Mice Mice, Inbred NOD Mice, Inbred Strains Mice, Knockout Mice, SCID Mice, Transgenic Natural Cytotoxicity Triggering Receptor 1 (genetics, metabolism) Natural Killer T-Cells (immunology) Receptors, Natural Cytotoxicity Triggering (immunology, metabolism) Xenograft Model Antitumor Assays

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!