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论文题目: Type I interferons exert anti-tumor effect via reversing immunosuppression mediated by mesenchymal stromal cells
英文论文题目: Type I interferons exert anti-tumor effect via reversing immunosuppression mediated by mesenchymal stromal cells
第一作者: Shou, P; Chen, Q; Jiang, J; Xu, C; Zhang, J; Zheng, C; Jiang, M; Velletri, T; Cao, W; Huang, Y; Yang, Q; Han, X; Zhang, L; Wei, L; Rabson, AB; Chin, YE; Wang, Y; Shi, Y
英文第一作者: Shou, P; Chen, Q; Jiang, J; Xu, C; Zhang, J; Zheng, C; Jiang, M; Velletri, T; Cao, W; Huang, Y; Yang, Q; Han, X; Zhang, L; Wei, L; Rabson, AB; Chin, YE; Wang, Y; Shi, Y
联系作者: Wang, Y (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
英文联系作者: Wang, Y (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
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发表年度: 2016
卷: 35
期: 46
页码: 5953-5962
摘要: Mesenchymal stromal cells (MSCs) are strongly immunosuppressive via producing nitric oxide (NO) and known to migrate into tumor sites to promote tumor growth, but the underlying mechanisms remain largely elusive. Here, we found that interferon alpha (IFN alpha)-secreting MSCs showed more dramatic inhibition effect on tumor progression than that of IFN alpha alone. Interestingly, IFN alpha primed MSCs could also effectively suppress tumor growth. Mechanistically, we demonstrated that both IFN alpha and IFN beta (type I IFNs) reversed the immunosuppressive effect of MSCs on splenocyte proliferation. This effect of type I IFNs was exerted through inhibiting inducible NO synthase (iNOS) expression in IFN. and TNFa-stimulated MSCs. Notably, only NO production was inhibited by IFN alpha; production of other cytokines or chemokines tested was not suppressed. Furthermore, IFN alpha promoted the switch from signal transducer and activator of transcription 1 (Stat1) homodimers to Stat1-Stat2 heterodimers. Studies using the luciferase reporter system and chromatin immunoprecipitation assay revealed that IFN alpha suppressed iNOS transcription through inhibiting the binding of Stat1 to iNOS promoter. Therefore, the synergistic anti-tumor effects of type I IFNs and MSCs were achieved by inhibiting NO production. This study provides essential information for understanding the mechanisms of MSC-mediated immunosuppression and for the development of better clinical strategies using IFNs and MSCs for cancer immunotherapy.
英文摘要: Mesenchymal stromal cells (MSCs) are strongly immunosuppressive via producing nitric oxide (NO) and known to migrate into tumor sites to promote tumor growth, but the underlying mechanisms remain largely elusive. Here, we found that interferon alpha (IFN alpha)-secreting MSCs showed more dramatic inhibition effect on tumor progression than that of IFN alpha alone. Interestingly, IFN alpha primed MSCs could also effectively suppress tumor growth. Mechanistically, we demonstrated that both IFN alpha and IFN beta (type I IFNs) reversed the immunosuppressive effect of MSCs on splenocyte proliferation. This effect of type I IFNs was exerted through inhibiting inducible NO synthase (iNOS) expression in IFN. and TNFa-stimulated MSCs. Notably, only NO production was inhibited by IFN alpha; production of other cytokines or chemokines tested was not suppressed. Furthermore, IFN alpha promoted the switch from signal transducer and activator of transcription 1 (Stat1) homodimers to Stat1-Stat2 heterodimers. Studies using the luciferase reporter system and chromatin immunoprecipitation assay revealed that IFN alpha suppressed iNOS transcription through inhibiting the binding of Stat1 to iNOS promoter. Therefore, the synergistic anti-tumor effects of type I IFNs and MSCs were achieved by inhibiting NO production. This study provides essential information for understanding the mechanisms of MSC-mediated immunosuppression and for the development of better clinical strategies using IFNs and MSCs for cancer immunotherapy.
刊物名称: ONCOGENE
英文刊物名称: ONCOGENE
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学科: Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity
英文学科: Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity
影响因子: 7.519
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论文类别: Article
英文论文类别: Article
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