Immunosuppressive inflammation is an inherent characteristic of prognostically‐bad uveal melanoma.

Abstract

AbstractPurpose The presence of infiltrating immune cells in uveal melanoma is associated with poor prognosis. An analysis of the different functional phenotypes of the tumor‐infiltrating leukocytes (TIL) may help to gain insight in the role of these infiltrating immune cells.Methods The density of CD8+ (CD3+CD8+ T cells) and CD4+ (CD3+CD8− T cells) T lymphocytes, CD4+ regulatory T cells (Tregs; CD3+CD8‐Foxp3+ cells), CD68+ and CD68+CD163+ macrophages was evaluated by immunofluorescence histochemistry in 43 cases of uveal melanoma. The correlations between different parameters were analyzed and their presence compared to known morphologic, immunologic, cytogenetic and molecular prognostic variables.Results The presence of increased numbers of all T cell subsets was associated with an epithelioid cell type, monosomy 3, and the class 2 gene expression profile (GEP). The presence of TIL was very variable, but strong correlations were observed between the different types of TIL. The presence of Tregs was correlated with the presence of M2 macrophages.Conclusion Uveal melanoma with more malignant characteristics such as monosomy 3 and the class 2 GEP contained more TILs, which included Tregs. These data suggest that tumor‐intrinsic factors distinguishing bad from good melanoma probably control the initiation of inflammation, which involves infiltration of tumors by different lymphocytic and myeloid immune cell subtypes, and support the notion that immunosuppressive inflammation contributes to increased malignancy in high risk uveal melanoma cases.