title: Toll-like Receptors in Regulatory T Cells of Patients With Head and Neck Cancer.
abstract: OBJECTIVE
  to investigate the role of Toll-like receptor (TLR) signaling and T-regulatory (T-reg) cells in patients with head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  multicolor flow cytometry was used to study the frequency and phenotype of CD4(+)CD25(+)CD127(-) T-reg cells and CD4(+)CD25(-)CD127(+) T-effector (T-eff) cells in peripheral blood mononuclear cells (PBMCs).
  
  
  METHODS
  all patients were seen at the outpatient clinic at the Department of Otorhinolaryngology at the University of Duisburg-Essen from March 1, 2009, through December 31, 2009.
  
  
  METHODS
  eleven patients with HNSCC and 10 healthy donors (HDs) were studied. T-reg and T-eff cells were isolated from PBMCs using a magnetic bead-activated cell-sorting technique.
  
  
  METHODS
  proliferation of T-eff cells and suppressor activity of T-reg cells were assessed in functional assays after preincubation with the TLR4 ligand heat shock protein 60 or lipopolysaccharide in the presence or absence of neutralizing antibody against TLR4.
  
  
  RESULTS
  frequency of T-reg cells in PBMCs was strongly increased in patients with HNSCC vs HDs. Isolation of T-reg cells from PBMCs of patients with HNSCC showed a significantly higher expression of TLR4, TLR6, TLR9, and TLR10 compared with HDs, whereas TLR2 was not detectable. After incubation with heat shock protein 60 or lipopolysaccharide, the suppressive function of T-reg cells was significantly increased (1.14- and 1.44-fold, respectively), whereas the proliferation capacity of T-eff cells remained unchanged. This effect was reversed after TLR4 inhibition on T-reg cells.
  
  
  CONCLUSIONS
  the TLR ligation on T-reg cells may contribute to tumor-mediated immune suppression by enhancing their suppressive activity.
authors.affiliation: Department of Otorhinolaryngology, University of Duisburg-Essen, Hufelandstr 55, 45122 Essen, Germany.
authors.forename: Clarissa Anni
authors.initials: CA
authors.lastname: Wild
authors.forename: Sven
authors.initials: S
authors.lastname: Brandau
authors.forename: Monika
authors.initials: M
authors.lastname: Lindemann
authors.forename: Ramin
authors.initials: R
authors.lastname: Lotfi
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Hoffmann
authors.forename: Stephan
authors.initials: S
authors.lastname: Lang
authors.forename: Christoph
authors.initials: C
authors.lastname: Bergmann
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000276:immunology / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012189:Retrospective Studies; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D051193:Toll-Like Receptors / Q000097:blood* / Q000276:immunology
chemical_list: D014408:Biomarkers, Tumor; D051193:Toll-Like Receptors