title: Circulating immune cell and microRNA in patients with uveal melanoma developing metastatic disease.
abstract: BACKGROUND
  The immune response has been implicated in the control of uveal melanoma progression. Epigenetic mechanisms mediated by specific microRNAs (miRs) regulate immune responses.
  
  
  METHODS
  Blood was drawn from six patients with uveal melanoma followed from diagnosis, at which time there was no clinical or radiographic evidence of metastasis, until metastasis manifested. Circulating T cell, natural killer (NK), natural killer T (NKT), and myeloid suppressor cell populations were assessed by flow cytometry. CD3(+), CD15(+), and CD56(+) cells were isolated using immunomagnetic beads. Plasma and cellular levels of immune regulatory miRs were determined by quantitative polymerase chain reaction assays.
  
  
  RESULTS
  The development of metastasis was associated with decreases in circulating CD3(-)CD56(dim) NK cells and CD8(+) and double-negative CD3(+)CD56(+) NKT cells. ICOS(+)CD4(+)FoxP3(+) T regulatory cells and CD11b(+)CD14(-)CD15(+) myeloid suppressor cells increased. Plasma levels of miR-20a, 125b, 146a, 155, 181a, and 223 were higher in the study patients at diagnosis compared to controls. Plasma levels of miR-20a, 125b, 146a, 155, and 223 increased, and miR-181a decreased when metastasis manifested. Alterations in immune regulatory miRs were also observed in CD3(+), CD15(+), and CD56(+) cell populations.
  
  
  CONCLUSIONS
  The development of metastasis in uveal melanoma is associated with changes in immune effector and regulatory cells consistent with lessening tumor immune surveillance. These changes are associated with changes in plasma and cellular levels of immune regulatory miRs. The results may help guide uveal melanoma immunotherapy and biomarker development.
authors.affiliation: Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH, United States.
authors.forename: Susan
authors.initials: S
authors.lastname: Achberger
authors.affiliation: Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH, United States.
authors.forename: Wayne
authors.initials: W
authors.lastname: Aldrich
authors.affiliation: Department of Molecular Pathology, Cleveland Clinic Foundation, Cleveland, OH, United States.
authors.forename: Raymond
authors.initials: R
authors.lastname: Tubbs
authors.affiliation: Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, United States.
authors.forename: John W
authors.initials: JW
authors.lastname: Crabb
authors.affiliation: Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, United States.
authors.forename: Arun D
authors.initials: AD
authors.lastname: Singh
authors.affiliation: Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH, United States. Electronic address: triozzp@ccf.org.
authors.forename: Pierre L
authors.initials: PL
authors.lastname: Triozzi
mesh_terms: D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000473:pathology*; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D014604:Uveal Neoplasms / Q000097:blood* / Q000473:pathology*; D000098943:Uveal Melanoma
chemical_list: D035683:MicroRNAs
keywords: Biomarkers; Immune response; MicroRNA; Uveal melanoma