IL-37 induces anti-tumor immunity by indirectly promoting dendritic cell recruitment and activation in hepatocellular carcinoma
Yuan Liu,1,2,* Jing-Jing Zhao,1,2,* Zi-Qi Zhou,1,2 Qiu-Zhong Pan,1,2 Qian Zhu,1,2 Yan Tang,1,2 Jian-Chuan Xia,1,2 De-Sheng Weng1,21State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer C...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2019-07-01
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| Series: | Cancer Management and Research |
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| Online Access: | https://www.dovepress.com/il-37-induces-anti-tumor-immunity-by-indirectly-promoting-dendritic-ce-peer-reviewed-article-CMAR |
| _version_ | 1818269626745749504 |
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| author | Liu Y Zhao JJ Zhou ZQ Pan QZ Zhu Q Tang Y Xia JC Weng DS |
| author_facet | Liu Y Zhao JJ Zhou ZQ Pan QZ Zhu Q Tang Y Xia JC Weng DS |
| author_sort | Liu Y |
| collection | DOAJ |
| description | Yuan Liu,1,2,* Jing-Jing Zhao,1,2,* Zi-Qi Zhou,1,2 Qiu-Zhong Pan,1,2 Qian Zhu,1,2 Yan Tang,1,2 Jian-Chuan Xia,1,2 De-Sheng Weng1,21State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Biotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China*These authors contributed equally to this workIntroduction: IL-37 is a cytokine of IL-1 family that plays an important role in innate immunity and inflammation, and has been studied as a tumor suppressor in many cancers. However, it remains unclear whether IL-37 plays a regulatory role in tumor-infiltrating dendritic cells (DCs) in hepatocellular carcinoma (HCC).Materials and methods: We evaluated the relationship between IL-37 expression and tumor infiltration by DCs in 155 HCC samples through immunohistochemical analysis and Kaplan–Meier survival analysis. The effects of IL-37 on the anti-tumor activity of DCs were investigated by ELISA, flow cytometry, real-time quantitative PCR, cytotoxicity assays and tumorigenicity assays.Results: The expression level of IL-37 in HCC samples was positively correlated with the degree of CD1a+ DCs infiltration. The survival rates of patients with both a high expression of IL-37 and a high infiltration by CD1a+ DCs were significantly higher than those of patients with a low expression of IL-37 and a low infiltration by CD1a+ DCs. In vitro chemotaxis analysis indicated that HCC cells overexpressing IL-37 recruited more DCs by secreting higher levels of specific chemokines (eg, CCL3 and CCL20). In addition, IL-37 indirectly up-regulated the expression of major histocompatibility class II molecules, CD86 and CD40 on DCs by acting on tumor cells; IL-37 also indirectly enhanced the anti-tumor effect of T lymphocytes by stimulating DCs to secrete cytokines such as IL-2, IL-12, IL-12p70, interferon-α (IFN-α) and IFN-γ. Finally, overexpression IL-37 in HCC cells significantly delayed tumor growth and increased recruitment of CD11c+ DCs to tumor tissues was also revealed in vivo mouse model.Conclusion: DCs play an important role in IL-37 mediated anti-tumor immune responses in HCC, which may contribute to the development of novel cancer immunotherapeutic strategies.Keywords: IL-37, dendritic cells, antitumor immunity, hepatocellular carcinoma |
| first_indexed | 2024-12-12T20:57:23Z |
| format | Article |
| id | doaj.art-e9572c98f3da4dc1a5f85b3284cdf898 |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-12T20:57:23Z |
| publishDate | 2019-07-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-e9572c98f3da4dc1a5f85b3284cdf8982022-12-22T00:12:15ZengDove Medical PressCancer Management and Research1179-13222019-07-01Volume 116691670247218IL-37 induces anti-tumor immunity by indirectly promoting dendritic cell recruitment and activation in hepatocellular carcinomaLiu YZhao JJZhou ZQPan QZZhu QTang YXia JCWeng DSYuan Liu,1,2,* Jing-Jing Zhao,1,2,* Zi-Qi Zhou,1,2 Qiu-Zhong Pan,1,2 Qian Zhu,1,2 Yan Tang,1,2 Jian-Chuan Xia,1,2 De-Sheng Weng1,21State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Biotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China*These authors contributed equally to this workIntroduction: IL-37 is a cytokine of IL-1 family that plays an important role in innate immunity and inflammation, and has been studied as a tumor suppressor in many cancers. However, it remains unclear whether IL-37 plays a regulatory role in tumor-infiltrating dendritic cells (DCs) in hepatocellular carcinoma (HCC).Materials and methods: We evaluated the relationship between IL-37 expression and tumor infiltration by DCs in 155 HCC samples through immunohistochemical analysis and Kaplan–Meier survival analysis. The effects of IL-37 on the anti-tumor activity of DCs were investigated by ELISA, flow cytometry, real-time quantitative PCR, cytotoxicity assays and tumorigenicity assays.Results: The expression level of IL-37 in HCC samples was positively correlated with the degree of CD1a+ DCs infiltration. The survival rates of patients with both a high expression of IL-37 and a high infiltration by CD1a+ DCs were significantly higher than those of patients with a low expression of IL-37 and a low infiltration by CD1a+ DCs. In vitro chemotaxis analysis indicated that HCC cells overexpressing IL-37 recruited more DCs by secreting higher levels of specific chemokines (eg, CCL3 and CCL20). In addition, IL-37 indirectly up-regulated the expression of major histocompatibility class II molecules, CD86 and CD40 on DCs by acting on tumor cells; IL-37 also indirectly enhanced the anti-tumor effect of T lymphocytes by stimulating DCs to secrete cytokines such as IL-2, IL-12, IL-12p70, interferon-α (IFN-α) and IFN-γ. Finally, overexpression IL-37 in HCC cells significantly delayed tumor growth and increased recruitment of CD11c+ DCs to tumor tissues was also revealed in vivo mouse model.Conclusion: DCs play an important role in IL-37 mediated anti-tumor immune responses in HCC, which may contribute to the development of novel cancer immunotherapeutic strategies.Keywords: IL-37, dendritic cells, antitumor immunity, hepatocellular carcinomahttps://www.dovepress.com/il-37-induces-anti-tumor-immunity-by-indirectly-promoting-dendritic-ce-peer-reviewed-article-CMARInterleukin-37dendritic cellsantitumor immunityhepatocellular carcinoma |
| spellingShingle | Liu Y Zhao JJ Zhou ZQ Pan QZ Zhu Q Tang Y Xia JC Weng DS IL-37 induces anti-tumor immunity by indirectly promoting dendritic cell recruitment and activation in hepatocellular carcinoma Cancer Management and Research Interleukin-37 dendritic cells antitumor immunity hepatocellular carcinoma |
| title | IL-37 induces anti-tumor immunity by indirectly promoting dendritic cell recruitment and activation in hepatocellular carcinoma |
| title_full | IL-37 induces anti-tumor immunity by indirectly promoting dendritic cell recruitment and activation in hepatocellular carcinoma |
| title_fullStr | IL-37 induces anti-tumor immunity by indirectly promoting dendritic cell recruitment and activation in hepatocellular carcinoma |
| title_full_unstemmed | IL-37 induces anti-tumor immunity by indirectly promoting dendritic cell recruitment and activation in hepatocellular carcinoma |
| title_short | IL-37 induces anti-tumor immunity by indirectly promoting dendritic cell recruitment and activation in hepatocellular carcinoma |
| title_sort | il 37 induces anti tumor immunity by indirectly promoting dendritic cell recruitment and activation in hepatocellular carcinoma |
| topic | Interleukin-37 dendritic cells antitumor immunity hepatocellular carcinoma |
| url | https://www.dovepress.com/il-37-induces-anti-tumor-immunity-by-indirectly-promoting-dendritic-ce-peer-reviewed-article-CMAR |
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