IRF3 Knockout Results in Partial or Complete Rejection of Murine Mesothelioma
Background: Malignant pleural mesothelioma (MESO) has a poor prognosis despite aggressive treatment with surgery, radiation and chemotherapy, and novel therapeutic approaches are needed. IRF3 is a downstream molecule of the cGAS/STING signaling pathway, but its roles have not been investigated in ME...
Ausführliche Beschreibung
Autor*in: |
Masaya Aoki [verfasserIn] Licun Wu [verfasserIn] Junichi Murakami [verfasserIn] Yidan Zhao [verfasserIn] Hana Yun [verfasserIn] Marc de Perrot [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2021 |
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Schlagwörter: |
malignant pleural mesothelioma (MESO) |
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Übergeordnetes Werk: |
In: Journal of Clinical Medicine - MDPI AG, 2013, 10(2021), 21, p 5196 |
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Übergeordnetes Werk: |
volume:10 ; year:2021 ; number:21, p 5196 |
Links: |
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DOI / URN: |
10.3390/jcm10215196 |
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Katalog-ID: |
DOAJ075251000 |
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520 | |a Background: Malignant pleural mesothelioma (MESO) has a poor prognosis despite aggressive treatment with surgery, radiation and chemotherapy, and novel therapeutic approaches are needed. IRF3 is a downstream molecule of the cGAS/STING signaling pathway, but its roles have not been investigated in MESO. Methods: Various murine mesothelioma cell lines were inoculated into wild type (WT) and IRF3 knockout (IRF3KO) mice to compare tumor growth. AE17-bearing mice were treated with local radiotherapy (LRT) to evaluate the effect on tumor growth, and immune cell infiltration was analyzed by flow cytometry 20 days after tumor inoculation. TCGA data were used to examine the relationship between mRNA expression of IRF3 and genes of the cGAS/STING signaling cascade on prognosis in MESO. Correlations between gene expression of IRF3, cGAS/STING signaling pathway, and immune checkpoints were analyzed in TCGA MESO and our scRNA-Seq data from MESO patients. Results: In mouse mesothelioma models, AK7, RN5 and ZiP3 were completely rejected in IRF3KO mice 20 days after the tumor challenge. AE17tumor volume was slightly larger than WT mice around day 10 before shrinking and becoming significantly smaller than WT mice on day 20. LRT accelerated tumor shrinkage of AE17 tumors in IRF3KO mice. Compared with WT mice, the number of macrophages infiltrating the tumor of IRF3KO mice was significantly reduced, and CD4<sup<+</sup< T cells and CD8<sup<+</sup<IFNγ<sup<+</sup< T cells were significantly increased. TCGA data showed that <i<IRF3</i< expression was an unfavorable prognostic factor in MESO patients. <i<IRF3</i< expression, the cGAS/STING signaling pathway, and immune checkpoints were positively correlated. Conclusion: <i<IRF3</i< could play a critical role in the tumor immune microenvironment of MESO. | ||
650 | 4 | |a malignant pleural mesothelioma (MESO) | |
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10.3390/jcm10215196 doi (DE-627)DOAJ075251000 (DE-599)DOAJ5f605b1bd0c94dbb8682ab437b585836 DE-627 ger DE-627 rakwb eng Masaya Aoki verfasserin aut IRF3 Knockout Results in Partial or Complete Rejection of Murine Mesothelioma 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Malignant pleural mesothelioma (MESO) has a poor prognosis despite aggressive treatment with surgery, radiation and chemotherapy, and novel therapeutic approaches are needed. IRF3 is a downstream molecule of the cGAS/STING signaling pathway, but its roles have not been investigated in MESO. Methods: Various murine mesothelioma cell lines were inoculated into wild type (WT) and IRF3 knockout (IRF3KO) mice to compare tumor growth. AE17-bearing mice were treated with local radiotherapy (LRT) to evaluate the effect on tumor growth, and immune cell infiltration was analyzed by flow cytometry 20 days after tumor inoculation. TCGA data were used to examine the relationship between mRNA expression of IRF3 and genes of the cGAS/STING signaling cascade on prognosis in MESO. Correlations between gene expression of IRF3, cGAS/STING signaling pathway, and immune checkpoints were analyzed in TCGA MESO and our scRNA-Seq data from MESO patients. Results: In mouse mesothelioma models, AK7, RN5 and ZiP3 were completely rejected in IRF3KO mice 20 days after the tumor challenge. AE17tumor volume was slightly larger than WT mice around day 10 before shrinking and becoming significantly smaller than WT mice on day 20. LRT accelerated tumor shrinkage of AE17 tumors in IRF3KO mice. Compared with WT mice, the number of macrophages infiltrating the tumor of IRF3KO mice was significantly reduced, and CD4<sup<+</sup< T cells and CD8<sup<+</sup<IFNγ<sup<+</sup< T cells were significantly increased. TCGA data showed that <i<IRF3</i< expression was an unfavorable prognostic factor in MESO patients. <i<IRF3</i< expression, the cGAS/STING signaling pathway, and immune checkpoints were positively correlated. Conclusion: <i<IRF3</i< could play a critical role in the tumor immune microenvironment of MESO. malignant pleural mesothelioma (MESO) interferon regulatory factor 3 (IRF3) cGAS/STING signaling pathway IRF3 knockout (IRF3KO) immune checkpoints Medicine R Licun Wu verfasserin aut Junichi Murakami verfasserin aut Yidan Zhao verfasserin aut Hana Yun verfasserin aut Marc de Perrot verfasserin aut In Journal of Clinical Medicine MDPI AG, 2013 10(2021), 21, p 5196 (DE-627)718632478 (DE-600)2662592-1 20770383 nnns volume:10 year:2021 number:21, p 5196 https://doi.org/10.3390/jcm10215196 kostenfrei https://doaj.org/article/5f605b1bd0c94dbb8682ab437b585836 kostenfrei https://www.mdpi.com/2077-0383/10/21/5196 kostenfrei https://doaj.org/toc/2077-0383 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 21, p 5196 |
spelling |
10.3390/jcm10215196 doi (DE-627)DOAJ075251000 (DE-599)DOAJ5f605b1bd0c94dbb8682ab437b585836 DE-627 ger DE-627 rakwb eng Masaya Aoki verfasserin aut IRF3 Knockout Results in Partial or Complete Rejection of Murine Mesothelioma 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Malignant pleural mesothelioma (MESO) has a poor prognosis despite aggressive treatment with surgery, radiation and chemotherapy, and novel therapeutic approaches are needed. IRF3 is a downstream molecule of the cGAS/STING signaling pathway, but its roles have not been investigated in MESO. Methods: Various murine mesothelioma cell lines were inoculated into wild type (WT) and IRF3 knockout (IRF3KO) mice to compare tumor growth. AE17-bearing mice were treated with local radiotherapy (LRT) to evaluate the effect on tumor growth, and immune cell infiltration was analyzed by flow cytometry 20 days after tumor inoculation. TCGA data were used to examine the relationship between mRNA expression of IRF3 and genes of the cGAS/STING signaling cascade on prognosis in MESO. Correlations between gene expression of IRF3, cGAS/STING signaling pathway, and immune checkpoints were analyzed in TCGA MESO and our scRNA-Seq data from MESO patients. Results: In mouse mesothelioma models, AK7, RN5 and ZiP3 were completely rejected in IRF3KO mice 20 days after the tumor challenge. AE17tumor volume was slightly larger than WT mice around day 10 before shrinking and becoming significantly smaller than WT mice on day 20. LRT accelerated tumor shrinkage of AE17 tumors in IRF3KO mice. Compared with WT mice, the number of macrophages infiltrating the tumor of IRF3KO mice was significantly reduced, and CD4<sup<+</sup< T cells and CD8<sup<+</sup<IFNγ<sup<+</sup< T cells were significantly increased. TCGA data showed that <i<IRF3</i< expression was an unfavorable prognostic factor in MESO patients. <i<IRF3</i< expression, the cGAS/STING signaling pathway, and immune checkpoints were positively correlated. Conclusion: <i<IRF3</i< could play a critical role in the tumor immune microenvironment of MESO. malignant pleural mesothelioma (MESO) interferon regulatory factor 3 (IRF3) cGAS/STING signaling pathway IRF3 knockout (IRF3KO) immune checkpoints Medicine R Licun Wu verfasserin aut Junichi Murakami verfasserin aut Yidan Zhao verfasserin aut Hana Yun verfasserin aut Marc de Perrot verfasserin aut In Journal of Clinical Medicine MDPI AG, 2013 10(2021), 21, p 5196 (DE-627)718632478 (DE-600)2662592-1 20770383 nnns volume:10 year:2021 number:21, p 5196 https://doi.org/10.3390/jcm10215196 kostenfrei https://doaj.org/article/5f605b1bd0c94dbb8682ab437b585836 kostenfrei https://www.mdpi.com/2077-0383/10/21/5196 kostenfrei https://doaj.org/toc/2077-0383 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 21, p 5196 |
allfields_unstemmed |
10.3390/jcm10215196 doi (DE-627)DOAJ075251000 (DE-599)DOAJ5f605b1bd0c94dbb8682ab437b585836 DE-627 ger DE-627 rakwb eng Masaya Aoki verfasserin aut IRF3 Knockout Results in Partial or Complete Rejection of Murine Mesothelioma 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Malignant pleural mesothelioma (MESO) has a poor prognosis despite aggressive treatment with surgery, radiation and chemotherapy, and novel therapeutic approaches are needed. IRF3 is a downstream molecule of the cGAS/STING signaling pathway, but its roles have not been investigated in MESO. Methods: Various murine mesothelioma cell lines were inoculated into wild type (WT) and IRF3 knockout (IRF3KO) mice to compare tumor growth. AE17-bearing mice were treated with local radiotherapy (LRT) to evaluate the effect on tumor growth, and immune cell infiltration was analyzed by flow cytometry 20 days after tumor inoculation. TCGA data were used to examine the relationship between mRNA expression of IRF3 and genes of the cGAS/STING signaling cascade on prognosis in MESO. Correlations between gene expression of IRF3, cGAS/STING signaling pathway, and immune checkpoints were analyzed in TCGA MESO and our scRNA-Seq data from MESO patients. Results: In mouse mesothelioma models, AK7, RN5 and ZiP3 were completely rejected in IRF3KO mice 20 days after the tumor challenge. AE17tumor volume was slightly larger than WT mice around day 10 before shrinking and becoming significantly smaller than WT mice on day 20. LRT accelerated tumor shrinkage of AE17 tumors in IRF3KO mice. Compared with WT mice, the number of macrophages infiltrating the tumor of IRF3KO mice was significantly reduced, and CD4<sup<+</sup< T cells and CD8<sup<+</sup<IFNγ<sup<+</sup< T cells were significantly increased. TCGA data showed that <i<IRF3</i< expression was an unfavorable prognostic factor in MESO patients. <i<IRF3</i< expression, the cGAS/STING signaling pathway, and immune checkpoints were positively correlated. Conclusion: <i<IRF3</i< could play a critical role in the tumor immune microenvironment of MESO. malignant pleural mesothelioma (MESO) interferon regulatory factor 3 (IRF3) cGAS/STING signaling pathway IRF3 knockout (IRF3KO) immune checkpoints Medicine R Licun Wu verfasserin aut Junichi Murakami verfasserin aut Yidan Zhao verfasserin aut Hana Yun verfasserin aut Marc de Perrot verfasserin aut In Journal of Clinical Medicine MDPI AG, 2013 10(2021), 21, p 5196 (DE-627)718632478 (DE-600)2662592-1 20770383 nnns volume:10 year:2021 number:21, p 5196 https://doi.org/10.3390/jcm10215196 kostenfrei https://doaj.org/article/5f605b1bd0c94dbb8682ab437b585836 kostenfrei https://www.mdpi.com/2077-0383/10/21/5196 kostenfrei https://doaj.org/toc/2077-0383 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 21, p 5196 |
allfieldsGer |
10.3390/jcm10215196 doi (DE-627)DOAJ075251000 (DE-599)DOAJ5f605b1bd0c94dbb8682ab437b585836 DE-627 ger DE-627 rakwb eng Masaya Aoki verfasserin aut IRF3 Knockout Results in Partial or Complete Rejection of Murine Mesothelioma 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Malignant pleural mesothelioma (MESO) has a poor prognosis despite aggressive treatment with surgery, radiation and chemotherapy, and novel therapeutic approaches are needed. IRF3 is a downstream molecule of the cGAS/STING signaling pathway, but its roles have not been investigated in MESO. Methods: Various murine mesothelioma cell lines were inoculated into wild type (WT) and IRF3 knockout (IRF3KO) mice to compare tumor growth. AE17-bearing mice were treated with local radiotherapy (LRT) to evaluate the effect on tumor growth, and immune cell infiltration was analyzed by flow cytometry 20 days after tumor inoculation. TCGA data were used to examine the relationship between mRNA expression of IRF3 and genes of the cGAS/STING signaling cascade on prognosis in MESO. Correlations between gene expression of IRF3, cGAS/STING signaling pathway, and immune checkpoints were analyzed in TCGA MESO and our scRNA-Seq data from MESO patients. Results: In mouse mesothelioma models, AK7, RN5 and ZiP3 were completely rejected in IRF3KO mice 20 days after the tumor challenge. AE17tumor volume was slightly larger than WT mice around day 10 before shrinking and becoming significantly smaller than WT mice on day 20. LRT accelerated tumor shrinkage of AE17 tumors in IRF3KO mice. Compared with WT mice, the number of macrophages infiltrating the tumor of IRF3KO mice was significantly reduced, and CD4<sup<+</sup< T cells and CD8<sup<+</sup<IFNγ<sup<+</sup< T cells were significantly increased. TCGA data showed that <i<IRF3</i< expression was an unfavorable prognostic factor in MESO patients. <i<IRF3</i< expression, the cGAS/STING signaling pathway, and immune checkpoints were positively correlated. Conclusion: <i<IRF3</i< could play a critical role in the tumor immune microenvironment of MESO. malignant pleural mesothelioma (MESO) interferon regulatory factor 3 (IRF3) cGAS/STING signaling pathway IRF3 knockout (IRF3KO) immune checkpoints Medicine R Licun Wu verfasserin aut Junichi Murakami verfasserin aut Yidan Zhao verfasserin aut Hana Yun verfasserin aut Marc de Perrot verfasserin aut In Journal of Clinical Medicine MDPI AG, 2013 10(2021), 21, p 5196 (DE-627)718632478 (DE-600)2662592-1 20770383 nnns volume:10 year:2021 number:21, p 5196 https://doi.org/10.3390/jcm10215196 kostenfrei https://doaj.org/article/5f605b1bd0c94dbb8682ab437b585836 kostenfrei https://www.mdpi.com/2077-0383/10/21/5196 kostenfrei https://doaj.org/toc/2077-0383 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 21, p 5196 |
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10.3390/jcm10215196 doi (DE-627)DOAJ075251000 (DE-599)DOAJ5f605b1bd0c94dbb8682ab437b585836 DE-627 ger DE-627 rakwb eng Masaya Aoki verfasserin aut IRF3 Knockout Results in Partial or Complete Rejection of Murine Mesothelioma 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Malignant pleural mesothelioma (MESO) has a poor prognosis despite aggressive treatment with surgery, radiation and chemotherapy, and novel therapeutic approaches are needed. IRF3 is a downstream molecule of the cGAS/STING signaling pathway, but its roles have not been investigated in MESO. Methods: Various murine mesothelioma cell lines were inoculated into wild type (WT) and IRF3 knockout (IRF3KO) mice to compare tumor growth. AE17-bearing mice were treated with local radiotherapy (LRT) to evaluate the effect on tumor growth, and immune cell infiltration was analyzed by flow cytometry 20 days after tumor inoculation. TCGA data were used to examine the relationship between mRNA expression of IRF3 and genes of the cGAS/STING signaling cascade on prognosis in MESO. Correlations between gene expression of IRF3, cGAS/STING signaling pathway, and immune checkpoints were analyzed in TCGA MESO and our scRNA-Seq data from MESO patients. Results: In mouse mesothelioma models, AK7, RN5 and ZiP3 were completely rejected in IRF3KO mice 20 days after the tumor challenge. AE17tumor volume was slightly larger than WT mice around day 10 before shrinking and becoming significantly smaller than WT mice on day 20. LRT accelerated tumor shrinkage of AE17 tumors in IRF3KO mice. Compared with WT mice, the number of macrophages infiltrating the tumor of IRF3KO mice was significantly reduced, and CD4<sup<+</sup< T cells and CD8<sup<+</sup<IFNγ<sup<+</sup< T cells were significantly increased. TCGA data showed that <i<IRF3</i< expression was an unfavorable prognostic factor in MESO patients. <i<IRF3</i< expression, the cGAS/STING signaling pathway, and immune checkpoints were positively correlated. Conclusion: <i<IRF3</i< could play a critical role in the tumor immune microenvironment of MESO. malignant pleural mesothelioma (MESO) interferon regulatory factor 3 (IRF3) cGAS/STING signaling pathway IRF3 knockout (IRF3KO) immune checkpoints Medicine R Licun Wu verfasserin aut Junichi Murakami verfasserin aut Yidan Zhao verfasserin aut Hana Yun verfasserin aut Marc de Perrot verfasserin aut In Journal of Clinical Medicine MDPI AG, 2013 10(2021), 21, p 5196 (DE-627)718632478 (DE-600)2662592-1 20770383 nnns volume:10 year:2021 number:21, p 5196 https://doi.org/10.3390/jcm10215196 kostenfrei https://doaj.org/article/5f605b1bd0c94dbb8682ab437b585836 kostenfrei https://www.mdpi.com/2077-0383/10/21/5196 kostenfrei https://doaj.org/toc/2077-0383 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 21, p 5196 |
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Masaya Aoki |
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IRF3 Knockout Results in Partial or Complete Rejection of Murine Mesothelioma malignant pleural mesothelioma (MESO) interferon regulatory factor 3 (IRF3) cGAS/STING signaling pathway IRF3 knockout (IRF3KO) immune checkpoints |
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irf3 knockout results in partial or complete rejection of murine mesothelioma |
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IRF3 Knockout Results in Partial or Complete Rejection of Murine Mesothelioma |
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Background: Malignant pleural mesothelioma (MESO) has a poor prognosis despite aggressive treatment with surgery, radiation and chemotherapy, and novel therapeutic approaches are needed. IRF3 is a downstream molecule of the cGAS/STING signaling pathway, but its roles have not been investigated in MESO. Methods: Various murine mesothelioma cell lines were inoculated into wild type (WT) and IRF3 knockout (IRF3KO) mice to compare tumor growth. AE17-bearing mice were treated with local radiotherapy (LRT) to evaluate the effect on tumor growth, and immune cell infiltration was analyzed by flow cytometry 20 days after tumor inoculation. TCGA data were used to examine the relationship between mRNA expression of IRF3 and genes of the cGAS/STING signaling cascade on prognosis in MESO. Correlations between gene expression of IRF3, cGAS/STING signaling pathway, and immune checkpoints were analyzed in TCGA MESO and our scRNA-Seq data from MESO patients. Results: In mouse mesothelioma models, AK7, RN5 and ZiP3 were completely rejected in IRF3KO mice 20 days after the tumor challenge. AE17tumor volume was slightly larger than WT mice around day 10 before shrinking and becoming significantly smaller than WT mice on day 20. LRT accelerated tumor shrinkage of AE17 tumors in IRF3KO mice. Compared with WT mice, the number of macrophages infiltrating the tumor of IRF3KO mice was significantly reduced, and CD4<sup<+</sup< T cells and CD8<sup<+</sup<IFNγ<sup<+</sup< T cells were significantly increased. TCGA data showed that <i<IRF3</i< expression was an unfavorable prognostic factor in MESO patients. <i<IRF3</i< expression, the cGAS/STING signaling pathway, and immune checkpoints were positively correlated. Conclusion: <i<IRF3</i< could play a critical role in the tumor immune microenvironment of MESO. |
abstractGer |
Background: Malignant pleural mesothelioma (MESO) has a poor prognosis despite aggressive treatment with surgery, radiation and chemotherapy, and novel therapeutic approaches are needed. IRF3 is a downstream molecule of the cGAS/STING signaling pathway, but its roles have not been investigated in MESO. Methods: Various murine mesothelioma cell lines were inoculated into wild type (WT) and IRF3 knockout (IRF3KO) mice to compare tumor growth. AE17-bearing mice were treated with local radiotherapy (LRT) to evaluate the effect on tumor growth, and immune cell infiltration was analyzed by flow cytometry 20 days after tumor inoculation. TCGA data were used to examine the relationship between mRNA expression of IRF3 and genes of the cGAS/STING signaling cascade on prognosis in MESO. Correlations between gene expression of IRF3, cGAS/STING signaling pathway, and immune checkpoints were analyzed in TCGA MESO and our scRNA-Seq data from MESO patients. Results: In mouse mesothelioma models, AK7, RN5 and ZiP3 were completely rejected in IRF3KO mice 20 days after the tumor challenge. AE17tumor volume was slightly larger than WT mice around day 10 before shrinking and becoming significantly smaller than WT mice on day 20. LRT accelerated tumor shrinkage of AE17 tumors in IRF3KO mice. Compared with WT mice, the number of macrophages infiltrating the tumor of IRF3KO mice was significantly reduced, and CD4<sup<+</sup< T cells and CD8<sup<+</sup<IFNγ<sup<+</sup< T cells were significantly increased. TCGA data showed that <i<IRF3</i< expression was an unfavorable prognostic factor in MESO patients. <i<IRF3</i< expression, the cGAS/STING signaling pathway, and immune checkpoints were positively correlated. Conclusion: <i<IRF3</i< could play a critical role in the tumor immune microenvironment of MESO. |
abstract_unstemmed |
Background: Malignant pleural mesothelioma (MESO) has a poor prognosis despite aggressive treatment with surgery, radiation and chemotherapy, and novel therapeutic approaches are needed. IRF3 is a downstream molecule of the cGAS/STING signaling pathway, but its roles have not been investigated in MESO. Methods: Various murine mesothelioma cell lines were inoculated into wild type (WT) and IRF3 knockout (IRF3KO) mice to compare tumor growth. AE17-bearing mice were treated with local radiotherapy (LRT) to evaluate the effect on tumor growth, and immune cell infiltration was analyzed by flow cytometry 20 days after tumor inoculation. TCGA data were used to examine the relationship between mRNA expression of IRF3 and genes of the cGAS/STING signaling cascade on prognosis in MESO. Correlations between gene expression of IRF3, cGAS/STING signaling pathway, and immune checkpoints were analyzed in TCGA MESO and our scRNA-Seq data from MESO patients. Results: In mouse mesothelioma models, AK7, RN5 and ZiP3 were completely rejected in IRF3KO mice 20 days after the tumor challenge. AE17tumor volume was slightly larger than WT mice around day 10 before shrinking and becoming significantly smaller than WT mice on day 20. LRT accelerated tumor shrinkage of AE17 tumors in IRF3KO mice. Compared with WT mice, the number of macrophages infiltrating the tumor of IRF3KO mice was significantly reduced, and CD4<sup<+</sup< T cells and CD8<sup<+</sup<IFNγ<sup<+</sup< T cells were significantly increased. TCGA data showed that <i<IRF3</i< expression was an unfavorable prognostic factor in MESO patients. <i<IRF3</i< expression, the cGAS/STING signaling pathway, and immune checkpoints were positively correlated. Conclusion: <i<IRF3</i< could play a critical role in the tumor immune microenvironment of MESO. |
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21, p 5196 |
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IRF3 Knockout Results in Partial or Complete Rejection of Murine Mesothelioma |
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https://doi.org/10.3390/jcm10215196 https://doaj.org/article/5f605b1bd0c94dbb8682ab437b585836 https://www.mdpi.com/2077-0383/10/21/5196 https://doaj.org/toc/2077-0383 |
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Licun Wu Junichi Murakami Yidan Zhao Hana Yun Marc de Perrot |
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