Cytokine profiles in the aqueous humor of uveal melanoma: implications for tumor progression and radiation response

Purpose This study aimed to investigate the cytokine profile in the aqueous humor of uveal melanoma (UM) and explore the role of cytokines in tumor progression and radiation response. Methods Aqueous humor samples were collected from patients with UM who had undergone enucleation or radiotherapy. Cytokine levels in these samples were measured using the Human 48-Plex Luminex assay, and statistical analyses were performed to evaluate the correlations with clinicopathological parameters. Results Thirty-six patients with UM were enrolled in this study: 17 in the enucleation group and 19 in the radiotherapy group. Significant differences in cytokine levels were observed between the two groups. The enucleation group exhibited higher levels of basic fibroblast growth factor (basic-FGF), interleukin-2 (IL-2), interleukin-2 receptor alpha (IL-2Rα), interleukin-12 subunit p40 (IL-12(P40)), macrophage colony-stimulating factor (M-CSF), macrophage migration inhibitory factor (MIF) than the radiotherapy group. Correlation analysis revealed significant associations between several cytokines and clinicopathological features, including tumor height, diameter, and treatment strategy. Tumor height was correlated with cytokines such as interleukin-8 (IL-8), M-CSF, and stem cell growth factor-beta (SCGF-β), while tumor diameter showed negative correlations with beta-nerve growth factor (β-NGF) and tumor necrosis factor-beta (TNF-β). Cytokines, including basic-FGF, IL-2, and MIF, were positively associated with radiation complications, while cytokines such as β-NGF, interleukin-12 subunit p70 (IL-12(P70)), and vascular endothelial growth factor (VEGF) exhibited negative correlations with post-radiation duration. Interleukin-5 (IL-5) was the only cytokine linked to subretinal fluid, and multiple cytokines, such as M-CSF and MIF, were correlated with the tumor cell type. Multiple regression analysis confirmed that these cytokines, including interferon-gamma (IFN-γ), interleukin-1 receptor antagonist (IL-1ra) and VEGF, were significantly associated with tumor characteristics and treatment response. Conclusion These findings suggest the potential role of cytokines in the tumor microenvironment of UM. The analysis points to these cytokines as possible biomarkers for tumor progression and treatment response. Further exploration of cytokines in the aqueous humor may enhance our understanding of UM and provide insights for managing post-treatment complications.