Targeting of tumour-infiltrating macrophages via CCL2/CCR2 signalling as a therapeutic strategy against hepatocellular carcinoma
文献类型：期刊论文
| 作者 | Li, Xiaoguang1; Yao, Wenbo1; Yuan, Ya1; Chen, Peizhan1; Li, Jingquan1; Chu, Ruiai1; Song, Haiyun1,4; Xie, Dong1,4; Wang, Hui1,3,4; Li, Bin2 |
| 刊名 | GUT
 |
| 出版日期 | 2017 |
| 卷号 | 66期号:1页码:157-167 |
| 关键词 | rice gas exchange photosynthetic property in situ high efficiency all-weather photosynthetic measurement system |
| ISSN号 | 0017-5749 |
| DOI | 10.1136/gutjnl-2015-310514 |
| 文献子类 | Article |
| 英文摘要 | Objective Hepatocellular carcinoma (HCC) is an aggressive malignancy with limited effective treatment options. An alternative strategy is to target cells, such as tumour-infiltrating macrophages, in the HCC tumour microenvironment. The CCL2/CCR2 axis is required for recruitment of monocytes/macrophages and is implicated in various aspects of liver pathology, including HCC. We investigated the feasibility of CCL2/CCR2 as a therapeutic target against HCC. Design CCL2 expression was analysed in two independent HCC cohorts. Growth of three murine HCC cells was evaluated in an orthotopic model, a postsurgical recurrence model and a subcutaneous model in mice after blocking CCL2/CCR2 axis by a novel CCR2 antagonist or knocking out of host CCR2. In vivo macrophage or T cell depletion and in vitro cell coculture were further conducted to investigate CCL2/CCR2-mediated crosstalk between tumour-associated macrophages (TAMs) and tumour cells. Result CCL2 is overexpressed in human liver cancers and is prognostic for patients with HCC. Blockade of CCL2/CCR2 signalling with knockout of CCR2 or with a CCR2 antagonist inhibits malignant growth and metastasis, reduces postsurgical recurrence, and enhances survival. Further, therapeutic blocking of the CCL2/CCR2 axis inhibits the recruitment of inflammatory monocytes, infiltration and M2-polarisation of TAMs, resulting in reversal of the immunosuppression status of the tumour microenvironment and activation of an antitumorous CD8(+) T cell response. Conclusions In patients with liver cancer, CCL2 is highly expressed and is a prognostic factor. Blockade of CCL2/CCR2 signalling suppresses murine liver tumour growth via activating T cell antitumour immune response. The results demonstrate the translational potential of CCL2/CCR2 blockade for treatment of HCCs. |
| 学科主题 | Gastroenterology & Hepatology |
| WOS关键词 | MOTIF LIGAND 2 ; PROSTATE-CANCER ; INFLAMMATORY MONOCYTES ; POOR-PROGNOSIS ; LIVER ; CCL2 ; METASTASIS ; CELLS ; MICROENVIRONMENT ; INHIBITION |
| 语种 | 英语 |
| WOS记录号 | WOS:000392282900019 |
| 出版者 | BMJ PUBLISHING GROUP |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/969]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab food safety Res, Shanghai, Peoples R China; 2.Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Shanghai, Peoples R China; 3.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China, 4.Minist Hlth, Key Lab food safety risk Assessment, Beijing, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Li, Xiaoguang,Yao, Wenbo,Yuan, Ya,et al. Targeting of tumour-infiltrating macrophages via CCL2/CCR2 signalling as a therapeutic strategy against hepatocellular carcinoma[J]. GUT,2017,66(1):157-167. |
| APA | Li, Xiaoguang.,Yao, Wenbo.,Yuan, Ya.,Chen, Peizhan.,Li, Jingquan.,...&,.(2017).Targeting of tumour-infiltrating macrophages via CCL2/CCR2 signalling as a therapeutic strategy against hepatocellular carcinoma.GUT,66(1),157-167. |
| MLA | Li, Xiaoguang,et al."Targeting of tumour-infiltrating macrophages via CCL2/CCR2 signalling as a therapeutic strategy against hepatocellular carcinoma".GUT 66.1(2017):157-167. |
入库方式： OAI收割
来源：上海营养与健康研究所
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