A positive-feedback loop between tumour infiltrating activated Treg cells and type 2-skewed macrophages is essential for progression of laryngeal squamous cell carcinoma.
A positive-feedback loop between tumour infiltrating activated Treg cells and type 2-skewed macrophages is essential for progression of laryngeal squamous cell carcinoma.
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肿瘤浸润的活化 Treg 细胞和 2 型偏态巨噬细胞之间的正反馈环对于喉鳞状细胞癌的进展至关重要。
DOI：
10.1038/bjc.2017.329
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发表时间：
2017-11-21
影响因子：
8.8
通讯作者：
Wen WP
中科院分区：
文献类型：
--
作者：
Sun W;Wei FQ;Li WJ;Wei JW;Zhong H;Wen YH;Lei WB;Chen L;Li H;Lin HQ;Iqbal M;Wen WP
Foxp3+ 调节性 T (Treg) 细胞和 M2 巨噬细胞与肿瘤进展加速相关。然而，Treg 细胞和 M2 巨噬细胞之间的相互作用仍不清楚。采用免疫组化方法检测65例喉鳞状细胞癌（LSCC）组织中FoxP3和CD163的表达情况。在体外，通过流式细胞术和 ELISA 分析通过与其前体细胞相互作用产生活化的 Treg (aTreg) 细胞和 M2 巨噬细胞。在体内，通过联合靶向aTreg细胞和M2巨噬细胞评估抗肿瘤效果，并通过流式细胞术分析瘤内免疫细胞。在 LSCC 组织中，aTreg 细胞和 M2 巨噬细胞的积累预示着不良预后，并且彼此呈正相关。在体外，aTreg 细胞是由癌细胞激活的 M2 样巨噬细胞从 CD4+CD25−T 细胞诱导而来。因此，这些 aTreg 细胞使单核细胞向 M2 样表型分化，从而形成正反馈回路。联合靶向 aTreg 细胞和 M2 巨噬细胞可在体内产生有效的抗肿瘤免疫。 aTreg细胞和M2巨噬细胞之间的正反馈环对于维持或促进肿瘤微环境中的免疫抑制至关重要，并且可能是抑制肿瘤进展的潜在治疗靶点。
Foxp3+ regulatory T (Treg) cells and M2 macrophages are associated with increased tumour progression. However, the interaction between Treg cells and M2 macrophages remains unclear. The expression of FoxP3 and CD163 was detected by immunohistochemistry in 65 cases of laryngeal squamous cell carcinoma (LSCC). In vitro, the generation of activated Treg (aTreg) cells and M2 macrophages by interactions with their precursor cells were analysed by flow cytometry and ELISA. In vivo, the antitumour effects were assessed by combined targeting aTreg cells and M2 macrophages, and intratumoural immunocytes were analysed by flow cytometry. In LSCC tissue, accumulation of aTreg cells and M2 macrophages predicted a poor prognosis and were positively associated with each other. In vitro, aTreg cells were induced from CD4+CD25− T cells by cancer cell-activated M2-like macrophages. Consequently, these aTreg cells skewed the differentiation of monocytes towards an M2-like phenotype, thereby forming a positive-feedback loop. Combined targeting aTreg cells and M2 macrophages led to potent antitumour immunity in vivo. The positive-feedback loop between aTreg cells and M2 macrophages is essential to maintain or promote immunosuppression in the tumour microenvironment and may be a potential therapeutic target to inhibit tumour progression.
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DOI：
10.4049/jimmunol.0802664
发表时间：
2009-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Liu Z;Kim JH;Falo LD Jr;You Z
通讯作者：
You Z
影响因子：
11.5
作者：
Badoual, C;Hans, S;Tartour, E
通讯作者：
Tartour, E
影响因子：
4.8
作者：
Kindt, Nadege;Descamps, Geraldine;Saussez, Sven
通讯作者：
Saussez, Sven
影响因子：
45.3
作者：
Chen, JJW;Lin, YC;Yang, PC
通讯作者：
Yang, PC
DOI：
10.1161/atvbaha.113.300168
发表时间：
2013-07-01
影响因子：
8.7
作者：
Mantovani, Alberto;Locati, Massimo
通讯作者：
Locati, Massimo