Enrichment of KIR+CD57+ highly cytotoxic NK cells in sentinel lymph nodes of melanoma patients

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POSTER PRESENTATION

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Enrichment of KIR+CD57+ highly cytotoxic NK cells in sentinel lymph nodes of melanoma patients Talib Hassan Ali1,2, Simona Pisanti3, Elena Ciaglia3, Roberta Mortarini4, Andrea Anichini4, Mario Santinami4, Elio Gulletta1, Caterina Ietto1, Mario Galgani5, Cinzia Garofalo1, Giuseppe Matarese5,6, Maurizio Bifulco3, Soldano Ferrone7, Francesco Colucci8, Alessandro Moretta9, Klas Kärre10, Ennio Carbone1,10* From Melanoma Bridge meeting 2013 Naples, Italy. 5-8 December 2013 Background NK cells contribute to melanoma cell recognition and anti-tumor immunity, which is traditionally analyzed using human peripheral blood NK cells. An important checkpoint in the progression of malignant melanoma is the metastasis to lymph nodes. Materials and methods To investigate the role of lymph node NK cells in disease progression, we analyzed frequency, phenotype and functions of NK cells purified from either tumor infiltrated lymph nodes or tumor-free ipsilateral lymph nodes of the same patients. Lymph node NK cells were compared to peripheral blood NK cells from either melanoma patients or healthy donors. Results The data showed an expansion of CD56dimCD57+CD69 +CCR7+KIR+ NK cells in tumor infiltrated lymph nodes. This phenotype corresponds to a recently described fully mature and highly cytotoxic NK cell population, and indeed we found that these lymph node NK cells displayed robust anti-tumor activity against autologous melanoma cells. The NK cells trafficking from periphery to the tumor draining lymph nodes have been investigated and the chemokines pattern identified. Moreover, the presence of a high proportion of KIR+CD57+CD56dim in the infiltrated lymph nodes was associated with an improved patients’ survival.

Conclusions Our data suggest that NK cells from tumor infiltrated lymph nodes are attractive candidates to improve current NK cell-based immunotherapy of melanoma. Authors’ details 1 Department of Experimental and Clinical Medicine “G. Salvatore”, University of Catanzaro ‘Magna Graecia’, Catanzaro, Italy. 2Department of Microbiology, College of Medicine, University of Thi-Qar, Nasseriah, Iraq. 3Department of Pharmaceutical and Biomedical Sciences, University of Salerno, Salerno, Italy. 4 Human Tumors Immunobiology Unit, Dept. of Experimental Oncology and Molecular Medicine (R.M. and A.A.), and Melanoma and Sarcoma Unit, Dept. of Surgery (M.S.), Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 5 Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), Naples, Italy. 6Department of Medicine, University of Salerno, Salerno, Italy. 7Department of Surgery, Immunology and Pathology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA. 8Department of Obstetrics and Gynaecology, University of Cambridge Clinical School, Cambridge, UK. 9Lab. of Molecular Immunology, Department of Experimental Medicine, University of Genova, Genova, Italy. 10Department of Microbiology Tumor and Cell Biology, Karolinska Institute, Stockholm, S