Analysis of Inflammatory Cells in Uveal Melanoma after Prior Irradiation

Abstract

Primary uveal melanomas with a poor prognosis contain high numbers of infiltrating macrophages, especially of the M2 phenotype, as well as lymphocytes. We wondered whether local inflammatory responses were affected by irradiation and therefore determined the presence of inflammatory cells in uveal melanomas enucleated after prior irradiation. We analyzed 46 uveal melanoma-containing eyes that had to be enucleated due to nonresponsiveness, tumor recurrence, or complications. Immunofluorescent staining was performed to determine the presence of CD68(+) and CD68(+)CD163(+) macrophages, and of CD4(+), CD8(+), and Foxp3(+) regulatory T lymphocytes. Outcomes were compared with clinical and histologic parameters. Numbers of CD68(+) and CD68(+)CD163(+) macrophages in secondarily enucleated eyes varied widely, but did not differ from primarily enucleated eyes and were not related to the reason for enucleation. Similarly, the number of CD4(+), CD8(+), and Foxp3(+) T lymphocytes showed great variability. Tumors with epithelioid cells showed significantly more lymphocytes than spindle cell tumors. In the first 2 years after enucleation, previously irradiated tumors showed increased numbers of lymphocytes compared with primarily enucleated eyes. Numbers of infiltrating T lymphocytes and macrophages varied widely between tumors, but tumors with high numbers of macrophages also contained more lymphocytes. Irradiation had no effect on the number and type of macrophages, but led to an increased amount of T lymphocytes up to 24 months postirradiation. Because the presence of infiltrating cells was related to the tumor cell type, it is conceivable that the presence of an infiltrate is especially a consequence of the primary tumor characteristics before irradiation.