Enrichment of CD56dimKIR+CD57+ highly cytotoxic NK cells in tumour-infiltrated lymph nodes of melanoma patients

Talib Hassan Ali, Simona Pisanti, Elena Ciaglia, Roberta Mortarini, Andrea Anichini, Cinzia Garofalo, Rossana Tallerico, Mario Santinami, Elio Gulletta, Caterina Ietto, Mario Galgani, Giuseppe Matarese, Maurizio Bifulco, Soldano Ferrone, Francesco Colucci, Alessandro Moretta, Klas Kärre and Ennio Carbone ()
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Talib Hassan Ali: University of Catanzaro ‘Magna Graecia’
Simona Pisanti: University of Salerno, Baronissi Campus
Elena Ciaglia: University of Salerno, Baronissi Campus
Roberta Mortarini: Human Tumors Immunobiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori
Andrea Anichini: Human Tumors Immunobiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori
Cinzia Garofalo: University of Catanzaro ‘Magna Graecia’
Rossana Tallerico: University of Catanzaro ‘Magna Graecia’
Mario Santinami: Melanoma and Sarcoma Unit, Fondazione IRCCS Istituto Nazionale dei Tumori
Elio Gulletta: University of Catanzaro ‘Magna Graecia’
Caterina Ietto: University of Catanzaro ‘Magna Graecia’
Mario Galgani: Istituto di Endocrinologia e Oncologia Sperimentale, IEOS-CNR, Università di Napoli Federico II
Giuseppe Matarese: University of Salerno, Baronissi Campus
Maurizio Bifulco: University of Salerno, Baronissi Campus
Soldano Ferrone: Harvard Medical School
Francesco Colucci: University of Cambridge Clinical School, NIHR Cambridge Biomedical Research Centre
Alessandro Moretta: Laboratory of Molecular Immunology, University of Genova
Klas Kärre: Karolinska Institute
Ennio Carbone: University of Catanzaro ‘Magna Graecia’

Nature Communications, 2014, vol. 5, issue 1, 1-9

Abstract: 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 CD56dimCD57dimCD69+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.

Date: 2014
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DOI: 10.1038/ncomms6639

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