Cytokines and chemokines in the vitreous fluid of eyes with uveal melanoma

Abstract

Purpose: In uveal melanoma, both tumor size and an inflammatory phenotype have been shown to correlate with a poor clinical prognosis. The purpose of this study was to identify whether inflammatory cytokines were present in the vitreous of eyes with uveal melanoma and to determine whether the vitreal concentration of cytokines correlated with prognostic variables such as tumor dimensions and immune cell infiltrate.

Methods: Vitreous was acquired from patients with uveal melanoma (n = 33) and from control eyes with no known ocular conditions (n = 9), and analyzed using a 27-plex cytokine bead array. Immunofluorescence testing was performed to determine the presence of macrophages, CD4(+), CD8(+), and Foxp3(+) regulatory T cells (T(regs)).

Results: Compared with control eyes, eyes with uveal melanoma demonstrated higher vitreal concentrations of many cytokines and chemokines, including IL-6, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β, TNF-α, and RANTES. IL-1ra was decreased in the vitreous of tumor-bearing eyes compared with controls. Tumor prominence positively correlated with several cytokines, including IL-6, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β, TNF-α, RANTES, GCSF, IFN-γ, and VEGF. IL-6 and IP-10 were found to positively correlate with increasing regulatory T-cell infiltrate and IL-6 alone positively correlated with macrophage infiltration.

Conclusions: Eyes with uveal melanoma contain higher vitreal concentrations of several inflammatory cytokines and chemokines that correlate predominantly with increasing tumor size; elevations in certain cytokines and chemokines also correlate with the presence of immune cell infiltrate.