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...
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Autor*in:	Masaya Aoki [verfasserIn] Licun Wu [verfasserIn] Junichi Murakami [verfasserIn] Yidan Zhao [verfasserIn] Hana Yun [verfasserIn] Marc de Perrot [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	malignant pleural mesothelioma (MESO) interferon regulatory factor 3 (IRF3) cGAS/STING signaling pathway IRF3 knockout (IRF3KO) immune checkpoints

Übergeordnetes Werk:	In: Journal of Clinical Medicine - MDPI AG, 2013, 10(2021), 21, p 5196
Übergeordnetes Werk:	volume:10 ; year:2021 ; number:21, p 5196

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/jcm10215196

Katalog-ID:	DOAJ075251000

Internformat


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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)
650		4	\|a interferon regulatory factor 3 (IRF3)
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author_variant	m a ma l w lw j m jm y z yz h y hy m d p mdp
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allfields	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
allfieldsSound	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
language	English
source	In Journal of Clinical Medicine 10(2021), 21, p 5196 volume:10 year:2021 number:21, p 5196
sourceStr	In Journal of Clinical Medicine 10(2021), 21, p 5196 volume:10 year:2021 number:21, p 5196
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topic_facet	malignant pleural mesothelioma (MESO) interferon regulatory factor 3 (IRF3) cGAS/STING signaling pathway IRF3 knockout (IRF3KO) immune checkpoints Medicine R
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authorswithroles_txt_mv	Masaya Aoki @@aut@@ Licun Wu @@aut@@ Junichi Murakami @@aut@@ Yidan Zhao @@aut@@ Hana Yun @@aut@@ Marc de Perrot @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
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author	Masaya Aoki
spellingShingle	Masaya Aoki misc malignant pleural mesothelioma (MESO) misc interferon regulatory factor 3 (IRF3) misc cGAS/STING signaling pathway misc IRF3 knockout (IRF3KO) misc immune checkpoints misc Medicine misc R IRF3 Knockout Results in Partial or Complete Rejection of Murine Mesothelioma
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topic_title	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
topic	misc malignant pleural mesothelioma (MESO) misc interferon regulatory factor 3 (IRF3) misc cGAS/STING signaling pathway misc IRF3 knockout (IRF3KO) misc immune checkpoints misc Medicine misc R
topic_unstemmed	misc malignant pleural mesothelioma (MESO) misc interferon regulatory factor 3 (IRF3) misc cGAS/STING signaling pathway misc IRF3 knockout (IRF3KO) misc immune checkpoints misc Medicine misc R
topic_browse	misc malignant pleural mesothelioma (MESO) misc interferon regulatory factor 3 (IRF3) misc cGAS/STING signaling pathway misc IRF3 knockout (IRF3KO) misc immune checkpoints misc Medicine misc R
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hierarchy_parent_title	Journal of Clinical Medicine
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title	IRF3 Knockout Results in Partial or Complete Rejection of Murine Mesothelioma
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title_full	IRF3 Knockout Results in Partial or Complete Rejection of Murine Mesothelioma
author_sort	Masaya Aoki
journal	Journal of Clinical Medicine
journalStr	Journal of Clinical Medicine
lang_code	eng
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publishDateSort	2021
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author_browse	Masaya Aoki Licun Wu Junichi Murakami Yidan Zhao Hana Yun Marc de Perrot
container_volume	10
format_se	Elektronische Aufsätze
author-letter	Masaya Aoki
doi_str_mv	10.3390/jcm10215196
author2-role	verfasserin
title_sort	irf3 knockout results in partial or complete rejection of murine mesothelioma
title_auth	IRF3 Knockout Results in Partial or Complete Rejection of Murine Mesothelioma
abstract	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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container_issue	21, p 5196
title_short	IRF3 Knockout Results in Partial or Complete Rejection of Murine Mesothelioma
url	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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author2	Licun Wu Junichi Murakami Yidan Zhao Hana Yun Marc de Perrot
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up_date	2024-07-03T13:50:58.343Z
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