Increased regulatory T-cell frequencies in patients with advanced melanoma correlate with a generally impaired T-cell responsiveness and are restored after dendritic cell-based vaccination.
Naturally occurring CD4(+) CD25(+) regulatory T-cell (Treg) activity is assumed to facilitate tumor development and progression. To elucidate the possible role of Tregs in the course of melanoma progression, we analysed the frequency of Tregs in the peripheral blood of patients at melanoma stages I-IV and in patients at melanoma stage IV that underwent dendritic cell (DC)-based immunotherapy. Using CD25, Foxp3, CD127 and HLA-DR as Treg associated markers, we observed increased Treg frequencies in patients at the late melanoma stage (stage IV) when compared to healthy donors. Accumulation of Tregs in patients with progressed melanoma correlated with a general reduction of T-cell responsiveness to the recall antigens tetanus toxoid and tuberculin-GT. However, DC-based immunotherapy not only restored antigen-specific immunity, but also decreased the frequency of Tregs in peripheral blood of patients with melanoma. These findings indicate that tumor progression in patients with melanoma result in general immunosuppression that is associated with Treg expansion in the periphery and can be overcome by DC-based vaccination.
Correll
Anita
A
Department of Dermatology, Universitätsmedizin Mainz, Johannes Gutenberg-University, Mainz, Germany.
Tuettenberg
Andrea
A
Becker
Christian
C
Jonuleit
Helmut
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002452:Cell Count; D018450:Disease Progression; D005260:Female; D051858:Forkhead Transcription Factors; D006684:HLA-DR Antigens; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D007801:Langerhans Cells / Q000276:immunology / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D008875:Middle Aged; D009367:Neoplasm Staging; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016896:Treatment Outcome
D019496:Cancer Vaccines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006684:HLA-DR Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit