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An increased level of interleukin-6 (IL-6) in epithelial ovarian cancer (EOC) is correlated with a worse prognosis. IL-6 stimulates tumor-growth and inflammation. We investigated the intricate interaction between the IL-6 signaling pathway and tumor-infiltrating myeloid cells (TIMs) to determine their prognostic impact in EOC. 160 EOC samples were analyzed for the expression of IL-6, its receptor (IL-6R) and downstream signaling via pSTAT3 by immunohistochemistry. Triple color immunofluorescence confocal microscopy was used to identify myeloid cell populations by CD14, CD33, and CD163. The relationship between these markers, tumor-infiltrating immune cells, clinical-pathological characteristics and survival was investigated. EOC displayed a dense infiltration with myeloid cells, in particular of the CD163+type. The distribution pattern of all myeloid subtypes was comparable among the different histological subtypes. Analysis of the tumor cells revealed a high expression of IL-6R in 15% and of IL-6 in 23% of patients. Interestingly, tumors expressing IL-6 or IL-6R formed two different groups. Tumors with a high expression of IL-6R displayed low mature myeloid cell infiltration and a longer disease-specific survival (DSS), especially in late stage tumors. High expression of IL-6R was an independent prognostic factor for survival by multivariate analyses (hazard ratio = 0.474,p= 0.011). In contrast, tumors with high epithelial IL-6 expression displayed a dense infiltration of mature myeloid cells and were correlated with a shorter DSS. Furthermore, in densely CD8+T-cell infiltrated tumors, the ratio between these lymphoid cells and CD163+myeloid cells was predictive for survival. Thus, IL-6 and IL-6R are opposite markers for myeloid cell infiltration and survival. [ABSTRACT FROM PUBLISHER]

Purpose 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. [ABSTRACT FROM AUTHOR]