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

Authors

  • Amit Mahipal
    • Department of Medical OncologyThomas Jefferson University
  • Mizue Terai
    • Department of Medical OncologyThomas Jefferson University
    • Department of Molecular and Tumor PathologyChiba University Graduate School of Medicine
  • David Berd
    • Cancer Treatment Centers of America, Eastern Regional Medical Center
  • Inna Chervoneva
    • Division of BiostatisticsThomas Jefferson University
  • Kashyap Patel
    • Carolina Blood and Cancer Care Associates
  • Michael J. Mastrangelo
    • Department of Medical OncologyThomas Jefferson University
    • Department of Medical OncologyThomas Jefferson University
Original article

DOI: 10.1007/s00262-011-1019-1

Cite this article as:
Mahipal, A., Terai, M., Berd, D. et al. Cancer Immunol Immunother (2011) 60: 1039. doi:10.1007/s00262-011-1019-1

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

Copyright information

© Springer-Verlag 2011