title: Dendritic cell generation and CD4+ CD25high FOXP3+ regulatory t cells in human head and neck carcinoma during radio-chemotherapy.
abstract: BACKGROUND
  Regulatory T cells (Treg) and dendritic cells (DC) play an important role in tumor immunity and immune escape. However, their interplay and the effects of anti-cancer therapy on the human immune system are largely unknown.
  
  
  METHODS
  For DC generation, CD14⊃+ monocytes were enriched by immunomagnetic selection from peripheral blood of advanced head and neck squamous cell carcinoma (HNSCC) patients and differentiated into immature DC using GM-SCF and IL-4. DC maturation was induced by addition of TNFα. The frequency of CD4⊃+CD25⊃highFOXP3⊃+ Treg in HNSCC patients was analyzed before and after radio-chemotherapy (RCT) by four-color flow cytometry.
  
  
  RESULTS
  In HNSCC patients, the frequency of Treg (0.33 ± 0.06%) was significantly (p = 0.001) increased compared to healthy controls (0.11 ± 0.02%), whereas RCT had variable effects on the Treg frequency inducing its increase in some patients and decrease in others. After six days in culture, monocytes of all patients had differentiated into immature DC. However, DC maturation indicated by CD83 up-regulation (70.7 ± 5.5%) was successful only in a subgroup of patients and correlated well with lower frequencies of peripheral blood Treg in those patients.
  
  
  CONCLUSIONS
  The frequency of regulatory T cells is elevated in HNSCC patients and may be modulated by RCT. Monocyte-derived DC in HNSCC patients show a maturation deficiency ex vivo. Those preliminary data may have an impact on multimodality clinical trials integrating cellular immune modulation in patients with advanced HNSCC.
authors.affiliation: Department of Otorhinolaryngology, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany. patrick.schuler@uk-essen.de
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Schuler
authors.forename: V
authors.initials: V
authors.lastname: Börger
authors.forename: E
authors.initials: E
authors.lastname: Bölke
authors.forename: D
authors.initials: D
authors.lastname: Habermehl
authors.forename: C
authors.initials: C
authors.lastname: Matuschek
authors.forename: C A
authors.initials: CA
authors.lastname: Wild
authors.forename: J
authors.initials: J
authors.lastname: Greve
authors.forename: M
authors.initials: M
authors.lastname: Bas
authors.forename: B
authors.initials: B
authors.lastname: Schilling
authors.forename: C
authors.initials: C
authors.lastname: Bergmann
authors.forename: S
authors.initials: S
authors.lastname: Trellakis
authors.forename: W
authors.initials: W
authors.lastname: Budach
authors.forename: T
authors.initials: T
authors.lastname: Gauler
authors.forename: S
authors.initials: S
authors.lastname: Brandau
authors.forename: S
authors.initials: S
authors.lastname: Lang
authors.forename: T L
authors.initials: TL
authors.lastname: Whiteside
authors.forename: R V
authors.initials: RV
authors.lastname: Sorg
authors.forename: T K
authors.initials: TK
authors.lastname: Hoffmann
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000276:immunology* / Q000628:therapy; D002452:Cell Count; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000097:blood / Q000276:immunology* / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors