CD163+CD204+ tumor-associated macrophages contribute to T cell regulation via interleukin-10 and PD-L1 production in oral squamous cell carcinoma

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.

RACK1 promotes cancer progression by increasing the M2/M1 macrophage ratio via the NF‐κB pathway in oral squamous cell carcinoma

“…Oral squamous cell carcinoma has an intricate TME that includes immune cells. Among these cells, TAM (M2) are believed to participate in the development and progression of OSCC (Fujii et al , ; He et al , ; Kubota et al , ; Lei et al , ; Matsuoka et al , ; Sato‐Kaneko et al , ). Current studies of macrophages in OSCC are not thorough and are limited to IHC staining experiments.…”

“…Clinical and experimental evidence has shown that TAM promote the development and progression of most tumor types (Ruffell and Coussens, ; Tan et al , ). There are many macrophages in OSCC tissues, and TAM are also believed to participate in OSCC progression (Kubota and Moriyama, ; Petruzzi et al , ; Sun et al , ). The most commonly used markers for M1 macrophages are CD11c, CD80 and HLA‐DR.…”

Prognostic impact of the tumor immune microenvironment in synovial sarcoma

“…Meanwhile, it was reported that tumor-associated macrophages, especially CD163+ CD204+, expressed higher levels of PD-L1 than other macrophage subsets. 44,45 Furthermore, PD-L1 expression on dendritic cells and macrophages in the tumor microenvironment is important for immunosuppression and resistance to PD-1/PD-L1 blockade therapy. 44,46 In the present study, there was no correlation between the…”

HLA class II expression on tumor cells and low numbers of tumor‐associated macrophages predict clinical outcome in oropharyngeal cancer

“…In addition, CD68+ TAMs, commonly identified by the expression of CD163, CD206, or CD204, also sustain the development and progression of many tumors, including oropharyngeal cancer, by suppressing the cytotoxic activity of CD8+ T cells, and promoting angiogenesis and tumor cell migration …”

“…24 In addition, CD68+ TAMs, commonly identified by the expression of CD163, CD206, or CD204, 25 also sustain the development and progression of many tumors, including oropharyngeal cancer, by suppressing the cytotoxic activity of CD8+ T cells, and promoting angiogenesis and tumor cell migration. [26][27][28] In this retrospective study, we aim to obtain a comprehensive "immune signature" of the HPV-negative and HPVpositive OPSCCs using immunohistochemistry (IHC) and immunofluorescence (IF) techniques for HLA expression, the presence of innate and adaptive immune cells and explore their correlation with clinical outcome. Ultimately, with the implementation of univariate and multivariate analysis, we aim to find independent prognostic factors for DFS and DSS of OPSCC patients.…”