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T.H. Khanh Vu, Inge H.G. Bronkhorst, Mieke Versluis, Marina Marinkovic, Sjoerd G. van Duinen, Johannes Vrolijk, Gregorius P.M. Luyten, Martine J. Jager; A Comparison Of Inflammation In Uveal Melanoma With And Without Prior Irradiation. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3417.
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It has previously been shown, that uveal melanoma with a bad prognosis contain high numbers of infiltrating macrophages, especially of the M2 phenotype, and increased numbers of lymphocytes. We wondered whether local inflammatory response were affected by irradiation and we therefore determined the presence of inflammatory cells in uveal melanoma-containing eyes enucleated after prior irradiation. Enucleation was indicated due to tumor recurrence, non-responsiveness to prior irradiation, or radiation-related complications.
Forty-six eyes, previously treated with ruthenium-106 brachytherapy (with or without adjuvant transpupillary thermotherapy) or proton beam irradiation, had to be enucleated. Immunofluorescence staining was performed on paraffin sections to determine the presence of CD68+ and CD68+CD163+ macrophages, and of CD3+, CD8+ and Foxp3+ regulatory T lymphocytes. Outcomes were compared with known clinical and histological prognostic parameters.
Numbers of CD68+ and CD68+CD163+ macrophages in secondarily-enucleated eyes varied widely, but were not increased compared to primarily-enucleated eyes and were not related to the reason for enucleation. Similarly, the number of CD3+, CD8+ and Foxp3+ regulatory T lymphocytes showed great variability; secondarily-enucleated eyes contained higher numbers of lymphocytes (p<.02) than primarily-enucleated eyes. Irradiated eyes containing epithelioid cells contained significantly more lymphocytes than spindle cell tumors (p<.04).
Numbers of infiltrating T lymphocytes and macrophages varied widely between tumors, but tumors with high numbers of macrophages also carried high numbers of lymphocytes. Prior irradiation had no clear effect on the number and type of macrophages in uveal melanoma, but led to an increased influx of T cells. As the presence of an infiltrate was associated with the cell type of the tumor, it may be that the amount of immunosuppressive inflammatory infiltrate is a consequence of the characteristics of the primary tumor before irradiation, such as loss of one chromosome 3.
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