Tumor-associated neutrophils and macrophages interaction contributes to intrahepatic cholangiocarcinoma progression by activating STAT3
Background Tumor-associated neutrophils (TANs) and macrophages (TAMs) can each influence cancer growth and metastasis, but their combined effects in intrahepatic cholangiocarcinoma (ICC) remain unclear.Methods We explored the distributions of TANs and TAMs in patient-derived ICC samples by multiplex...
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BMJ Publishing Group
2021-03-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/9/3/e001946.full |
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| author | Jian Zhou Jia Fan Zhiqiang Hu Jia Li Zhengjun Zhou Pengcheng Wang Rongqi Sun Haoyang Xin Chubin Luo Shaolai Zhou |
| author_facet | Jian Zhou Jia Fan Zhiqiang Hu Jia Li Zhengjun Zhou Pengcheng Wang Rongqi Sun Haoyang Xin Chubin Luo Shaolai Zhou |
| author_sort | Jian Zhou |
| collection | DOAJ |
| description | Background Tumor-associated neutrophils (TANs) and macrophages (TAMs) can each influence cancer growth and metastasis, but their combined effects in intrahepatic cholangiocarcinoma (ICC) remain unclear.Methods We explored the distributions of TANs and TAMs in patient-derived ICC samples by multiplex immunofluorescent staining and tested their separate and combined effects on ICC in vitro and in vivo. We then investigated the mechanistic basis of the effects using PCR array, western blot analysis and ELISA experiments. Finally, we validated our results in a tissue microarray composed of primary tumor tissues from 359 patients with ICC.Results The spatial distributions of TANs and TAMs were correlated with each other in patient-derived ICC samples. Interaction between TANs and TAMs enhanced the proliferation and invasion abilities of ICC cells in vitro and tumor progression in a mouse xenograft model of ICC. TANs and TAMs produced higher levels of oncostatin M and interleukin-11, respectively, in co-culture than in monoculture. Both of those cytokines activated STAT3 signaling in ICC cells. Knockdown of STAT3 abolished the protumor effect of TANs and TAMs on ICC. In tumor samples from patients with ICC, increased TAN and TAM levels were correlated with elevated p-STAT3 expression. All three of those factors were independent predictors of patient outcomes.Conclusions TANs and TAMs interact to promote ICC progression by activating STAT3. |
| format | Article |
| id | doaj-art-4a2a9bfd52a64b569cab213c83e461a7 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2021-03-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-4a2a9bfd52a64b569cab213c83e461a72025-02-04T05:50:13ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262021-03-019310.1136/jitc-2020-001946Tumor-associated neutrophils and macrophages interaction contributes to intrahepatic cholangiocarcinoma progression by activating STAT3Jian Zhou0Jia Fan1Zhiqiang Hu2Jia Li3Zhengjun Zhou4Pengcheng Wang5Rongqi Sun6Haoyang Xin7Chubin Luo8Shaolai Zhou9Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, ChinaDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, ChinaDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, ChinaNational Clinical Research Center for Kidney Disease, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, ChinaDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, ChinaDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, ChinaDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, ChinaDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, ChinaBackground Tumor-associated neutrophils (TANs) and macrophages (TAMs) can each influence cancer growth and metastasis, but their combined effects in intrahepatic cholangiocarcinoma (ICC) remain unclear.Methods We explored the distributions of TANs and TAMs in patient-derived ICC samples by multiplex immunofluorescent staining and tested their separate and combined effects on ICC in vitro and in vivo. We then investigated the mechanistic basis of the effects using PCR array, western blot analysis and ELISA experiments. Finally, we validated our results in a tissue microarray composed of primary tumor tissues from 359 patients with ICC.Results The spatial distributions of TANs and TAMs were correlated with each other in patient-derived ICC samples. Interaction between TANs and TAMs enhanced the proliferation and invasion abilities of ICC cells in vitro and tumor progression in a mouse xenograft model of ICC. TANs and TAMs produced higher levels of oncostatin M and interleukin-11, respectively, in co-culture than in monoculture. Both of those cytokines activated STAT3 signaling in ICC cells. Knockdown of STAT3 abolished the protumor effect of TANs and TAMs on ICC. In tumor samples from patients with ICC, increased TAN and TAM levels were correlated with elevated p-STAT3 expression. All three of those factors were independent predictors of patient outcomes.Conclusions TANs and TAMs interact to promote ICC progression by activating STAT3.https://jitc.bmj.com/content/9/3/e001946.full |
| spellingShingle | Jian Zhou Jia Fan Zhiqiang Hu Jia Li Zhengjun Zhou Pengcheng Wang Rongqi Sun Haoyang Xin Chubin Luo Shaolai Zhou Tumor-associated neutrophils and macrophages interaction contributes to intrahepatic cholangiocarcinoma progression by activating STAT3 Journal for ImmunoTherapy of Cancer |
| title | Tumor-associated neutrophils and macrophages interaction contributes to intrahepatic cholangiocarcinoma progression by activating STAT3 |
| title_full | Tumor-associated neutrophils and macrophages interaction contributes to intrahepatic cholangiocarcinoma progression by activating STAT3 |
| title_fullStr | Tumor-associated neutrophils and macrophages interaction contributes to intrahepatic cholangiocarcinoma progression by activating STAT3 |
| title_full_unstemmed | Tumor-associated neutrophils and macrophages interaction contributes to intrahepatic cholangiocarcinoma progression by activating STAT3 |
| title_short | Tumor-associated neutrophils and macrophages interaction contributes to intrahepatic cholangiocarcinoma progression by activating STAT3 |
| title_sort | tumor associated neutrophils and macrophages interaction contributes to intrahepatic cholangiocarcinoma progression by activating stat3 |
| url | https://jitc.bmj.com/content/9/3/e001946.full |
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