Cancer Immunology, Immunotherapy

, Volume 60, Issue 7, pp 1039–1045

Tumor-derived interleukin-10 as a prognostic factor in stage III patients undergoing adjuvant treatment with an autologous melanoma cell vaccine

  • Amit Mahipal
  • Mizue Terai
  • David Berd
  • Inna Chervoneva
  • Kashyap Patel
  • Michael J. Mastrangelo
  • Takami Sato
Original article

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.

Keywords

Melanoma Interleukin-10 Cytokines Cancer vaccines Tumor markers 

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Amit Mahipal
    • 1
  • Mizue Terai
    • 1
    • 2
  • David Berd
    • 3
  • Inna Chervoneva
    • 4
  • Kashyap Patel
    • 5
  • Michael J. Mastrangelo
    • 1
  • Takami Sato
    • 1
  1. 1.Department of Medical OncologyThomas Jefferson UniversityPhiladelphiaUSA
  2. 2.Department of Molecular and Tumor PathologyChiba University Graduate School of MedicineChibaJapan
  3. 3.Cancer Treatment Centers of America, Eastern Regional Medical CenterPhiladelphiaUSA
  4. 4.Division of BiostatisticsThomas Jefferson UniversityPhiladelphiaUSA
  5. 5.Carolina Blood and Cancer Care AssociatesRock HillUSA

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