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

Authors

Amit Mahipal, Thomas Jefferson UniversityFollow
Mizue Terai, Thomas Jefferson UniversityFollow
David Berd, , Eastern Regional Medical Center, Philadelphia, PA.
Inna Chervoneva, Thomas Jefferson UniversityFollow
Kashyap Patel, Carolina Blood and Cancer Care Associates, Rock Hill, SC.
Michael Mastrangelo, Thomas Jefferson UniversityFollow
Takami Sato, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

7-1-2011

Comments

This article has been peer reviewed. It is the authors' final version prior to publication in Cancer Immunology, Immunotherapy

Volume 60, Issue 7, July 2011, Pages 1039-1045

The published version is available at DOI: 10.1007/s00262-011-1019-1. Copyright © Springer

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.

Recommended Citation

Mahipal, Amit; Terai, Mizue; Berd, David; Chervoneva, Inna; Patel, Kashyap; Mastrangelo, Michael; and Sato, Takami, "Tumor-derived interleukin-10 as a prognostic factor in stage III patients undergoing adjuvant treatment with an autologous melanoma cell vaccine." (2011). Department of Medical Oncology Faculty Papers. Paper 12.
https://jdc.jefferson.edu/medoncfp/12

PubMed ID

21519827