Prolonged survival of dendritic cell-vaccinated melanoma patients correlates with tumor-specific delayed type IV hypersensitivity response and reduction of tumor growth factor ?-expressing T cells

SALAZAR ONFRAY F; López, M N.; Pereda, C; Segal G; Munoz L.; Aguilera R.; Gonzalez V.E.; Escobar A.; Ginesta, A; Reyes, D; González R.; Mendoza-Naranjo, A; Larrondo M.; Compan A.; Ferrada C.

Keywords: growth, survival, population, follow-up, cytokine, cells, culture, antigen, cell, disease, patient, trial, beta, cancer, tumor, vaccines, humans, phase, human, male, melanoma, aged, hypersensitivity, delayed, progression, skin, neoplasms, fever, adult, female, immunization, headache, immune, vaccine, article, factor, production, recombinant, analysis, lymphocyte, anorexia, immunotherapy, follow, cd4, controlled, clinical, studies, lysate, study, staging, response, interleukin, priority, middle, journal, syndrome, 2, up, Hypersensitivity,, t, course, regulatory, transforming, dendritic, T-Lymphocytes,, like, Overall, flu

Abstract

Purpose The aim of this work was to assess immunologic response, disease progression, and posttreatment 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) j3+ 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+TGF/3+ regulatory T cells and in vivo antimelanoma immune response associated to improved patient survival and disease stability. © 2009 by American Society of Clinical Oncology.

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Título de la Revista: JOURNAL OF CLINICAL ONCOLOGY
Volumen: 27
Número: 6
Editorial: AMER SOC CLINICAL ONCOLOGY
Fecha de publicación: 2009
Página de inicio: 945
Página final: 952
URL: http://www.scopus.com/inward/record.url?eid=2-s2.0-60849084473&partnerID=q2rCbXpz