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F.M. Damico, A.M. Lane, E.S. Gragoudas, L.H. Y. Young; Ocular Melanoma Induces Secretion of Anti–Tumoral Cytokines and Is Associated With Serum Levels of VEGF and TGFß . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1007.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Ocular melanoma is the most common primary intraocular tumor in adults, and tumor–related death within 10 years of diagnosis may be as high as 60%. Peripheral cell–mediated immune response has been demonstrated in choroidal melanoma patients. Cytokines, as effectors of the cellular immune response, influence the capacity of the tumor to grow and metastasize. We evaluated the role of several pro– and anti–tumoral cytokines in the development of ocular melanoma. Methods: We measured pre–treatment serum levels of pro–tumoral (VEGF and bFGF) and anti–tumoral cytokines (TGFß, TNFα and IFNγ) by ELISA in 75 patients with ocular melanoma and 40 controls subjects without retinal disease, who were matched to patients on age and gender. Differences in the detection of cytokines in the serum were evaluated using Fisher’s exact test. Logistic regression was used to determine if cytokine levels were predictive of disease status. In the ocular melanoma patient group, we also assessed the relationship between cytokine levels and certain tumor and patient characteristics (linear transversal diameter, height, pigment, iris color) using Pearson and Spearman correlation. Results: IFNγ and TNFα were more commonly detected in patients (P=0.007 and P=0.04, respectively) than in control subjects. In multivariate regression, subjects with VEGF levels in the highest tertile (>701 pg/ml) were statistically significantly more likely to have melanoma (OR: 4.4, 95% CI: 1.5–12.9, P=0.007) than subjects with VEGF levels in the lowest tertile (≤264 pg/ml). For TGFß, higher serum levels appear to be protective: subjects with levels >7.8 ng/ml were at reduced odds of having melanoma (OR: 0.21, 95% CI: 0.07–0.60, P=0.004). There were no significant correlations found between tumor characteristics and levels of VEGF or TGFß. Conclusions: Ocular melanoma induces peripheral production of anti–tumoral cytokines IFNγ and TNFα. High serum levels of VEGF and low serum levels of TGFß are associated with ocular melanoma. These data may be useful for the development of adjuvant immunotherapy.
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