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J Clin Oncol ; 27(6): 945-52, 2009 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-19139436

RESUMO

PURPOSE: The aim of this work was to assess immunologic response, disease progression, and post-treatment survival of melanoma patients vaccinated with autologous dendritic cells (DCs) pulsed with a novel allogeneic cell lysate (TRIMEL) derived from three melanoma cell lines. PATIENTS AND METHODS: Forty-three stage IV and seven stage III patients were vaccinated four times with TRIMEL/DC vaccine. Specific delayed type IV hypersensitivity (DTH) reaction, ex vivo cytokine production, and regulatory T-cell populations were determined. Overall survival and disease progression rates were analyzed using Kaplan-Meier curves and compared with historical records. RESULTS: The overall survival for stage IV patients was 15 months. More than 60% of patients showed DTH-positive reaction against the TRIMEL. Stage IV/DTH-positive patients displayed a median survival of 33 months compared with 11 months observed for DTH-negative patients (P = .0014). All stage III treated patients were DTH positive and remained alive and tumor free for a median follow-up period of 48 months (range, 33 to 64 months). DTH-positive patients showed a marked reduction in the proportion of CD4+ transforming growth factor (TGF) beta+ regulatory T cells compared to DTH-negative patients (1.54% v 5.78%; P < .0001). CONCLUSION: Our findings strongly suggest that TRIMEL-pulsed DCs provide a standardized and widely applicable source of melanoma antigens, very effective in evoking antimelanoma immune response. To our knowledge, this is the first report describing a correlation between vaccine-induced reduction of CD4+TGFbeta+ regulatory T cells and in vivo antimelanoma immune response associated to improved patient survival and disease stability.


Assuntos
Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Melanoma/imunologia , Neoplasias Cutâneas/imunologia , Adulto , Progressão da Doença , Feminino , Seguimentos , Humanos , Hipersensibilidade Tardia/imunologia , Masculino , Melanoma/mortalidade , Melanoma/terapia , Pessoa de Meia-Idade , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/terapia , Análise de Sobrevida , Linfócitos T Reguladores/imunologia , Fator de Crescimento Transformador beta/biossíntese
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