CD206+ tumor-associated macrophages promote proliferation and invasion in oral squamous cell carcinoma via EGF production

Abstract

Tumor-associated macrophages (TAMs) promote tumor progression and inhibit anti-tumor immune response by producing various mediators and preferentially express CD163, CD204, and CD206. However, the role of these TAM subsets in oral squamous cell carcinoma (OSCC) remains unclear. Here we investigated the expression and function of TAM subsets in OSCC, especially in cancer cell proliferation. Biopsy sample from 44 patients with OSCC were examined for the expression of TAM markers and EGF by immunohistochemistry. EGF production of TAM subsets isolated from OSCC patients was assessed by flow cytometry. We also examined the effect of conditioned medium from TAM subsets on the proliferation of OSCC cells. CD163+ cells were detected diffusely all over the tumor and connective tissue area, while CD204+ and CD206+ cells were mainly detected in/around the tumors. Flow cytometric analysis found that CD206+ TAMs strongly produced EGF compared with CD163+ and CD204+ TAMs. Cell proliferation and invasion of OSCC cells cultured with conditioned medium of CD206+ TAMs were strongly enhanced and inhibited by anti-EGFR. The number of CD206+ TAMs positively correlated with worse clinical prognosis. Our results revealed differences in localization and EGF production among these TAM subsets. CD206+ TAMs might play a critical role in the proliferation of OSCC via EGF production.

Magnolol Attenuates Cisplatin-Induced Muscle Wasting by M2c Macrophage Activation

“…Unexpectedly, both mag and cis+mag groups showed significant decrease in the percentages of infiltrated tumor-associated macrophages compared to the con group, whereas there was no significant difference between the con and cis groups (Figures 8D-F). As CD206 + and CD163 + M2-like tumor-associated macrophages have been associated with tumor progression and poor clinical prognosis (33)(34)(35), we also verified whether magnolol increases M2-like tumor associated macrophages. We quantitated the percentages of CD206 + CD163 + M2-like subtypes in CD11b + F4/80 + tumor-associated macrophages and there was no significant difference among all groups (Figures 8G,H).…”

High dimensional immunotyping of the obese tumor microenvironment reveals model specific adaptation

“…Macrophages, identified by high expression of CD11b, F4/80, and MHC-II, fell into 6 metaclusters representing macrophages of differing phenotypes and function. CD206 expression is associated with an M2 or pro-tumor phenotype(Haque et al, 2019;Nawaz et al, 2017). CD11c hi macrophages (MC2) were phenotypically similar to an M1, known to be an anti-tumor phenotype macrophage(Gautier et al, 2012; Noy & Pollard, 2014;Zhu et al, 2017).…”

Contribution of Macrophages and T Cells in Skeletal Metastasis

“…One of the growth factors secreted by TAMs is the epidermal growth factor (EGF), which stimulates the expression of its receptor (EGFR) in breast cancer cells to continuously activate the signal transducer and activator of transcription 3 (STAT3)/SRY-Box Transcription Factor 2 (Sox-2) signaling pathway enhancing cancer cell survival and proliferation in mice [48][49][50]. This was confirmed by another study where the authors demonstrated that CD206 + (M2-like) TAMs secrete high levels of EGF in oral squamous cell carcinomas (OSCC), and that cell proliferation was increased in OSCC cells treated with conditioned media from CD206 + TAMs [51]. Further studies demonstrated that EGF produced by M2-like TAMs suppresses long non-coding RNA inhibiting metastasis (LIMT) expression to promote proliferation, migration, and invasion in ovarian cancer through the activation of EGFR-extracellular-signal-regulated kinase (ERK) signaling [52].…”