CD163(+)CD204(+) tumor-associated macrophages contribute to T cell regulation via interleukin-10 and PD-L1 production in oral squamous cell carcinoma.
CD163(+)CD204(+) tumor-associated macrophages contribute to T cell regulation via interleukin-10 and PD-L1 production in oral squamous cell carcinoma.
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DOI：
10.1038/s41598-017-01661-z
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发表时间：
2017-05-11
影响因子：
4.6
通讯作者：
Nakamura S
中科院分区：
文献类型：
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作者：
Kubota K;Moriyama M;Furukawa S;Rafiul HASM;Maruse Y;Jinno T;Tanaka A;Ohta M;Ishiguro N;Yamauchi M;Sakamoto M;Maehara T;Hayashida JN;Kawano S;Kiyoshima T;Nakamura S
肿瘤相关巨噬细胞（tumor associated macrophages, tam）通过产生多种介质促进癌细胞增殖、侵袭和转移。尽管临床前研究表明TAM优先表达CD163和CD204，但TAM在口腔鳞状细胞癌（OSCC）中的亚群仍然未知。在这项研究中，我们研究了TAM亚群在OSCC中的表达和作用。应用免疫组织化学方法分析46例OSCC患者活检标本中tam的表达情况。我们用流式细胞术检测了3例OSCC患者外周血单个核细胞中TAM亚群及其免疫抑制分子（IL-10和PD-L1）的产生。CD163在肿瘤或结缔组织周围检测到，CD204在肿瘤内或肿瘤周围检测到。流式细胞分析显示，与CD163+CD204 -和CD163 - CD204+ tam相比，CD163+CD204+ tam强烈产生IL-10和PD-L1。此外，与CD163+CD204+ TAM共培养后，活化的CD3+ T细胞数量明显低于与其他TAM亚群共培养后的活化细胞数量。临床发现，CD163+CD204+ tam数量与CD25+细胞数量和5年无进展生存期呈负相关。这些结果表明，CD163+CD204+ tam可能通过t细胞调节IL-10和PD-L1的产生，在OSCC的侵袭和转移中发挥关键作用。
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.