Interleukin-10 as a prognostic factor in patients treated with autologous melanoma cell vaccine.

Abstract

8588 Background: Interleukin-10 (IL-10) downregulates the T cell-mediated immune response. We studied the association between IL10 production by freshly isolated melanoma cell suspensions in vitro and overall survival in patients who were treated with cancer vaccine consisting of the same autologous melanoma cells modified with a hapten, dinitrophenyl (DNP). It was assumed that production of IL-10 in tumor cell suspensions reflect the degree of IL-10 in tumor microenvironment. Methods: Tumor cells were extracted from metastatic tissues and cryopreserved until vaccine production. Small fraction of melanoma cell suspensions were separated prior to vaccine production and cultured overnight for the production of IL-10 in the culture supernatants. After inactivation with radiation and modification with DNP, autologous melanoma cells were injected to patients as a cancer vaccine. The final vaccine products did not produce IL-10. Forty four patients including 29 stage III and 15 stage IV disease were evaluated. The cut-off of 200 pg/mL was used to differentiate high versus low IL-10 producers based on scattergram. Cox regression model was used for multivariate analysis. Overall survival was calculated using Kaplan and Meier method and survival curves were compared with log-rank tests. Results: Out of 44 patients, 29 were low and 15 were high IL-10 producers. The overall survival (OS) was significantly longer for low versus high IL-10 producers (median OS 42 vs. 10.5 months, p = 0.02). In stage III patients, median OS for low and high IL-10 producers was 84 months and 9.7 months respectively (p = 0.07). In stage IV patients, the corresponding values were 13.7 months and 10.5 months (0.62). In multivariate analysis, the hazard ratios for stage III and stage IV patients were 2.92 (1.04-8.20) and 0.92 (0.28-3.00). Conclusions: Our study suggests that high IL-10 production in tumor cells is associated with worse prognosis in stage III melanoma patients receiving autologous vaccine. It has been shown that delayed-type hypersensitivity to autologous tumor cells is associated with longer OS. By downregulating the T cell mediated immune response, IL-10 in tumor microenvironment may decrease the effectiveness of the vaccine. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AVAX