title: Tumor-derived interleukin-10 as a prognostic factor in stage III patients undergoing adjuvant treatment with an autologous melanoma cell vaccine.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Medical Oncology, Thomas Jefferson University, 1025 Walnut Street, Philadelphia, PA 19107, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Mahipal
authors.forename: Mizue
authors.initials: M
authors.lastname: Terai
authors.forename: David
authors.initials: D
authors.lastname: Berd
authors.forename: Inna
authors.initials: I
authors.lastname: Chervoneva
authors.forename: Kashyap
authors.initials: K
authors.lastname: Patel
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mastrangelo
authors.forename: Takami
authors.initials: T
authors.lastname: Sato
mesh_terms: D000276:Adjuvants, Immunologic; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000627:therapeutic use*; D005260:Female; D006241:Haptens; D006801:Humans; D006968:Hypersensitivity, Delayed; D016753:Interleukin-10 / Q000378:metabolism*; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015996:Survival Rate; D059016:Tumor Microenvironment
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D006241:Haptens; D016753:Interleukin-10