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

• DOI: 10.1038/ncomms6639
• Publication Date: 2014-12-04T11:26:53Z
• Authors: 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; Ennio Carbone
• Keywords: Adult; Antigens, Differentiation, T-Lymphocyte; Male; 0301 basic medicine; Receptors, CCR7; Skin Neoplasms; 610; Article; 03 medical and health sciences; CD57 Antigens; Antigens, CD; Humans; Lectins, C-Type; Melanoma; Aged; Middle Aged; Receptors, Interleukin-6; CD56 Antigen; 3. Good health; Killer Cells, Natural; Receptors, KIR2DL3; Lymphatic Metastasis; Receptors, KIR2DL2; CD56(dim)KIR+CD57+;cytotoxic NK;cells ; tumour;melanoma;patients;; Female; Lymph Nodes

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.