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

Abstract

ObjectiveAccumulating 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 methodsThe 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.ResultsTongue 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.ConclusionsIn tongue leukoplakia, CD163+ macrophages infiltration correlates with immunosuppressive cytokine IL‐10 expression.

Intraepithelial CD163+ macrophages in tongue leukoplakia biopsy: A promising tool for cancer screening

“…Several studies have shown that CD163 + macrophages influence the differences in the development of OSCC and the prognoses of patients with OSCC (Fujii et al, ; He et al, ; Troiano et al, ; Usami et al, ; Yamagata et al, ). We recently reported that the infiltration of CD163 + macrophages correlates with the immunosuppressive cytokine interleukin‐10 expression in tongue leukoplakia (TL) (Shigeoka, Koma, Nishio, Komori, & Yokozaki, ).…”

Tongue Cancer Cell-Derived CCL20 Induced by Interaction With Macrophages Promotes CD163 Expression on Macrophages

“…Therefore, there is sufficient evidence to support that CD163 is the most important TAM marker of TSCC. We also previously reported the CD163-positive macrophages related to the malignant behavior of oral precancerous lesions (21,22,70). By contrast, reliable human M1 macrophage markers for immunohistochemistry have not been established (6).…”

“…Numerous studies have proposed that CD163 is a TAM marker of OSCC ( 14 – 20 ). We showed in a previous report that subepithelial CD163-positive macrophages are associated with an immunosuppressive cytokine interleukin (IL)-10 secretion in tongue leukoplakia (TL), which is a common OPMD ( 21 ). In addition, we showed that the number of intraepithelial CD163-positive macrophages of TL with invasive carcinoma is remarkably higher than in noninvasive TL, based on immunohistochemical study using human clinical samples ( 22 ).…”

CD163+ Foamy Macrophages Are Associated with the Morphogenesis of Oral Verruciform Xanthoma through Angiogenesis by VEGF Expression: An Immunohistochemical Study

“…On the other hand, studies have reported a few rare cases of OVX associated with malignant lesions [36][37][38]. In addition, several investigators have reported about the correlation between CD163 + macrophages and epithelial dysplasia and the malignancy of oral precancerous lesions [13,14,39,40]. Therefore, we must not overlook the malignant potential of squamous epithelium within the OVXs, which are considered as benign reactive lesions.…”