Infiltrative T regulatory cells in enucleated uveal melanomas

Purpose: The role of T regulatory (Treg) cells in blunting immune response to cancer appears to be significant, but the presence of Treg cells in uveal melanoma has not been extensively examined. We therefore evaluated the presence of tumor-infiltrating Treg cells in uveal melanomas. Methods: A retrospective search of Mayo Clinic records from 2000 to 2005 was performed to identify cases of eyes enucleated as a consequence of uveal melanoma. Histologic examination included location of the tumor, presence of emissary canal invasion, direct sclera extension, extraocular extension, cell type and predominant cell type, mitotic figures per 40 high-power fields, lymphocytic tumor invasion, necrosis, microvascular pattern, and presence of CD3, CD4, CD25, and Foxp3cells. Factors obtained by chart review were also evaluated, including clinical size and ultrasound thickness of tumor before enucleation, patient age at time of enucleation, systemic evaluation for metastatic disease both before and after enucleation, monosomy 3, and systemic status at last patient visit. Results: Of 42 enucleated eyes, 17 (40.5 %) were found to have lymphocytic infiltrate and 5 (11.9%) were considered positive for the presence of Treg cells (CD3+CD4+CD25+Foxp3+ or CD3+CD4+CD25-Foxp3+). Thus 29.4% (5 of 17) of those with lymphocytic infiltates had Treg cells, and 4 of the 5 with Treg cells had a large lymphocytic infiltrate (>1400 CD3 cells). When using "death due to disease" as the hazard ratio (HR) end point, the HR for presence of CD3 was 5.5 (P = .03) and for clinical size, 1.2 (P = .03). Furthermore, when using "presence of metastasis" as the end point, the HR for presence of CD3 was 3.6 (P = .05) and for clinical size, 1.3 (P = .003). Conclusion: Though T lymphocyte infiltration is a bad prognostic indicator, Treg cells are rarely seen in enucleated choroidal melanoma, so their local effect may be limited in contradistinction to other cancers.