Abstract
Tumor-associated macrophages (TAMs) promote cancer cell proliferation, invasion, and metastasis by producing various mediators. Although preclinical studies demonstrated that TAMs preferentially express CD163 and CD204, the TAM subsets in oral squamous cell carcinoma (OSCC) remain unknown. In this study, we examined the expression and role of TAM subsets in OSCC. Forty-six patients with OSCC were analyzed for expression of TAMs in biopsy samples by immunohistochemistry. We examined TAM subsets and their production of immune suppressive molecules (IL-10 and PD-L1) in peripheral blood mononuclear cells from three OSCC patients by flow cytometry. CD163 was detected around the tumor or connective tissue, while CD204 was detected in/around the tumors. Flow cytometric analysis revealed that CD163+CD204+ TAMs strongly produced IL-10 and PD-L1 in comparison with CD163+CD204− and CD163−CD204+ TAMs. Furthermore, the number of activated CD3+ T cells after co-culture with CD163+CD204+ TAMs was significantly lower than that after co-culture with other TAM subsets. In clinical findings, the number of CD163+CD204+ TAMs was negatively correlated with that of CD25+ cells and 5-year progression-free survival. These results suggest that CD163+CD204+ TAMs possibly play a key role in the invasion and metastasis of OSCC by T-cell regulation via IL-10 and PD-L1 production.
Highlights
Monocytes/macrophages are important contributors to cancer-associated inflammation
We first performed immunohistochemical staining to evaluate the distribution of tumor-associated macrophage (TAM) (CD163, CD204) and activated immune cell markers (CD25 and CD69) in oral squamous cell carcinoma (OSCC) tissues
Macrophages are classified into two major subsets: classically activated (M1) macrophages stimulated by Th1-type responses and alternatively activated (M2) macrophages stimulated by Th2-type responses[6, 7]
Summary
Monocytes/macrophages are important contributors to cancer-associated inflammation. The heterogeneity of macrophages has been discussed with regard to different responses to various microenvironmental stimuli. Several studies have shown that M2 macrophages infiltrating into the tumor microenvironment contribute to cancer progression and are associated with tumor progression, angiogenesis, metastasis and immunosuppression. This macrophage phenotype is referred to as the tumor-associated macrophage (TAM)[5,6,7]. CD163 and CD204-positive macrophages are positively correlated with the histological gradient of malignancy in human ovarian tumors[8] and CD163 and CD204 are useful markers for activation of TAMs in human samples. In malignant lymphoma, glioma, and kidney cancer, higher CD163 expression on TAMs is associated with worse clinical prognosis; no correlation exists between clinical prognosis www.nature.com/scientificreports/. We examined the levels of immune suppressive molecules produced by each TAM subset (CD163+CD204+, CD163+CD204+, and CD163+CD204+ TAMs) and association with clinical outcome
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
