CD163(+) macrophages infiltration correlates with the immunosuppressive cytokine interleukin 10 expression in tongue leukoplakia

OBJECTIVE: Accumulating evidence suggests that macrophages are involved in the immunoediting of oral squamous cell carcinoma but the role of macrophages in oral carcinogenesis is unclear. We aimed to clarify the role of macrophages in oral leukoplakia, which is the most common oral potentially malignant disorder from immunotolerance viewpoint. MATERIALS AND METHODS: The study included 24 patients who underwent surgical resection for tongue leukoplakia. The relationships between macrophage markers and clinicopathological factors were assessed. Conditioned medium was harvested from the CD163(+) human monocytic leukaemia cell line, THP‐1. The phenotypic alteration of human oral keratinocytes by the conditioned medium treatment was assessed using quantitative reverse transcription‐polymerase chain reaction and enzyme‐linked immunosorbent assay. Moreover, the clinical samples were evaluated using immunohistochemistry. RESULTS: Tongue leukoplakia tissues with high CD163(+) macrophage infiltration were associated with significantly higher degrees of epithelial dysplasia, abnormal Ki‐67 expression and cytokeratin13 loss when compared with the tissues with low CD163(+) macrophage infiltration. In vitro, CD163(+) THP‐1 conditioned medium induced immunosuppressive molecules, especially interleukin‐10 (IL‐10) in human oral keratinocytes. The IL‐10 expression levels showed significant positive correlations with not only the numbers of FOXP3(+) regulatory T cells but also that of CD163(+) macrophages. CONCLUSIONS: In tongue leukoplakia, CD163(+) macrophages infiltration correlates with immunosuppressive cytokine IL‐10 expression.