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

Abstract

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.

• Authors: Mercedes N López, Cristian Pereda, Gabriela Segal, Leonel Muñoz, Raquel Aguilera, Fermín E González, Alejandro Escobar, Alexandra Ginesta, Diego Reyes, Rodrigo González, Ariadna Mendoza-Naranjo, Milton Larrondo, Alvaro Compán, Carlos Ferrada, Flavio Salazar-Onfray
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 27 Issue 6 Pg. 945-52 (Feb 20 2009) ISSN: 1527-7755 [Electronic] United States
• PMID: 19139436 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• Transforming Growth Factor beta

Topics

• Adult
• Cancer Vaccines (immunology)
• Dendritic Cells (immunology)
• Disease Progression
• Female
• Follow-Up Studies
• Humans
• Hypersensitivity, Delayed (immunology)
• Male
• Melanoma (immunology, mortality, therapy)
• Middle Aged
• Skin Neoplasms (immunology, mortality, therapy)
• Survival Analysis
• T-Lymphocytes, Regulatory (immunology)
• Transforming Growth Factor beta (biosynthesis)