Enrichment of CD56(dim)KIR + CD57 + highly cytotoxic NK cells in tumour-infiltrated lymph nodes of melanoma patients

Nat Commun. 2014 Dec 4;5:5639. doi: 10.1038/ncomms6639.

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 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • CD56 Antigen / metabolism
  • CD57 Antigens / metabolism
  • Female
  • Humans
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Lectins, C-Type / metabolism
  • Lymph Nodes / immunology*
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Male
  • Melanoma / immunology*
  • Melanoma / pathology
  • Middle Aged
  • Receptors, CCR7 / metabolism
  • Receptors, Interleukin-6 / metabolism
  • Receptors, KIR2DL2 / metabolism
  • Receptors, KIR2DL3 / metabolism
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / pathology
  • Tumor Microenvironment / immunology

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CCR7 protein, human
  • CD56 Antigen
  • CD57 Antigens
  • CD69 antigen
  • KIR2DL2 protein, human
  • KIR2DL3 protein, human
  • Lectins, C-Type
  • Receptors, CCR7
  • Receptors, Interleukin-6
  • Receptors, KIR2DL2
  • Receptors, KIR2DL3