Abstract
Objectives: Interleukin-10 (IL-10) downregulates T-cell-mediated immune responses. We studied the association between IL-10 production by freshly isolated melanoma cell suspensions in vitro and overall survival in patients undergoing adjuvant treatment with a vaccine prepared from the same autologous melanoma cells modified with a hapten, dinitrophenyl (DNP). Methods: Forty-four patients with cutaneous melanoma (29 stage III and 15 stage IV) were prospectively evaluated. Tumor cells were extracted from metastatic deposits for production of DNP-modified autologous melanoma cell vaccine. Small aliquots of the melanoma cell suspensions were separated prior to vaccine processing and cultured overnight for IL-10 production. Based on a blind assessment of the distribution of IL-10 levels in the culture supernatants, a cutoff of 200 pg/ml was used to define high versus low IL-10 producers. Cox regression model was used for multivariate analysis. Overall survival was calculated using the Kaplan-Meier method, and survival curves were compared with the log-rank test. Results: Out of 44 patients, 29 were low and 15 were high IL-10 producers. The median OS was significantly worse for high compared with low IL-10 producers (10.5 months vs. 42 months; P = 0.022). In stage III patients, the multivariate hazard ratio for high versus low IL-10 producers was 2.92 (95% CI, 1.04-8.20; P = 0.041). The corresponding hazard ratio in stage IV patients was 0.92 (95% CI, 1.04-8.20; P = 0.888). Conclusions: High IL-10 production in the tumor microenvironment could be a determinant of clinical outcomes in stage III melanoma patients receiving autologous melanoma cell vaccine.
Original language | English (US) |
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Pages (from-to) | 1039-1045 |
Number of pages | 7 |
Journal | Cancer Immunology, Immunotherapy |
Volume | 60 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2011 |
Keywords
- Cancer vaccines
- Cytokines
- Interleukin-10
- Melanoma
- Tumor markers
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Oncology
- Cancer Research