Specific knockout of Notch2 in Treg cells significantly inhibits the growth and proliferation of head and neck squamous cell carcinoma in mice

•Specific knockout of Notch2 gene in Treg cells can significantly inhibit the growth of HNSCC.•Specific knockout of Notch2 in Treg cells can significantly inhibit the function of Tregs and enhance the anti-HNSCC effect.•The tumor tissues had significant pyroptosis in Treg cell-specific Notch2-knocko...

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Published in:International immunopharmacology 2023-10, Vol.123, p.110705-110705, Article 110705
Main Authors: Wei, Jun-Hua, Qiao, Yue-long, Xu, Shan, Zou, You, Ni, Hai-Feng, Wu, Li-Zhi, Tao, Ze-Zhang, Jiao, Wo-Er, Chen, Shi-Ming
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Language:English
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Antitumor immunity
Head and neck squamous cell carcinoma
Knockout mice
Notch2
Regulatory T cells
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container_title International immunopharmacology
container_volume 123
creator Wei, Jun-Hua
Qiao, Yue-long
Xu, Shan
Zou, You
Ni, Hai-Feng
Wu, Li-Zhi
Tao, Ze-Zhang
Jiao, Wo-Er
Chen, Shi-Ming
description •Specific knockout of Notch2 gene in Treg cells can significantly inhibit the growth of HNSCC.•Specific knockout of Notch2 in Treg cells can significantly inhibit the function of Tregs and enhance the anti-HNSCC effect.•The tumor tissues had significant pyroptosis in Treg cell-specific Notch2-knockout mice. To investigate the effect of Notch2 gene knockout in Treg cells on head and neck squamous cell carcinoma (HNSCC) in mice. A mouse model of HNSCC was constructed. Flow cytometry and immunofluorescence were used to examine the numbers of related immune cells and programmed cell death in tumor cells in the spleen and tumor microenvironment of mice. Western blotting was used to measure the expression of related proteins in tumor tissues. The tumor volume of regulatory T (Treg) cell-specific Notch2-knockout mice (experimental group) was significantly smaller than that of control mice (control group) (P 
doi_str_mv 10.1016/j.intimp.2023.110705
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To investigate the effect of Notch2 gene knockout in Treg cells on head and neck squamous cell carcinoma (HNSCC) in mice. A mouse model of HNSCC was constructed. Flow cytometry and immunofluorescence were used to examine the numbers of related immune cells and programmed cell death in tumor cells in the spleen and tumor microenvironment of mice. Western blotting was used to measure the expression of related proteins in tumor tissues. The tumor volume of regulatory T (Treg) cell-specific Notch2-knockout mice (experimental group) was significantly smaller than that of control mice (control group) (P &lt; 0.05). Compared with those in the control group, the number of Treg cells and the expression of Ki67 in Treg cells in the spleen and tumor tissue were significantly decreased in the experimental group, while the numbers of CD45+ hematopoietic cells, CD4+ T cells, CD8+ T cells, T helper 1 (Th1) cells, CD11b+ cells (macrophages), and CD11b+CD11c+ cells (dendritic cells) and the expression of Ki67 in CD4+ T cells and CD8+ T cells were significantly increased (P &lt; 0.05). There was no significant difference in the number of Th2 cells between the two groups (P &gt; 0.05). Immunofluorescence analysis showed that the numbers of CD4+ T cells and CD8+ T cells in the tumor tissue in the experimental group were significantly higher than those in the control group (P &lt; 0.05). Compared with that in the control group, programmed cell death in the experimental group was significantly increased (P &lt; 0.05). Moreover, the expression levels of NLRP3, Caspase-1 and GSDMD in the tumor tissues of the experimental group were higher than those in the control group (P &lt; 0.01), while the expression levels of BCL2, Bax, ATG5, LC3 and p62 were not significantly different (P &gt; 0.05). Specific knockout of the Notch2 gene in Treg cells significantly decreases the function of Treg cells, inhibits the growth of HNSCC and improves the immune microenvironment in mice, thus effectively treating HNSCC.</description><identifier>ISSN: 1567-5769</identifier><identifier>EISSN: 1878-1705</identifier><identifier>DOI: 10.1016/j.intimp.2023.110705</identifier><identifier>PMID: 37523971</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Antitumor immunity ; Head and neck squamous cell carcinoma ; Knockout mice ; Notch2 ; Regulatory T cells</subject><ispartof>International immunopharmacology, 2023-10, Vol.123, p.110705-110705, Article 110705</ispartof><rights>2023 Elsevier B.V.</rights><rights>Copyright © 2023 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-fe04acf24828f82410c6068aec1235d6c2b6c41308c097b1afedb3c1ef6922003</citedby><cites>FETCH-LOGICAL-c362t-fe04acf24828f82410c6068aec1235d6c2b6c41308c097b1afedb3c1ef6922003</cites><orcidid>0000-0002-1216-004X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37523971$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wei, Jun-Hua</creatorcontrib><creatorcontrib>Qiao, Yue-long</creatorcontrib><creatorcontrib>Xu, Shan</creatorcontrib><creatorcontrib>Zou, You</creatorcontrib><creatorcontrib>Ni, Hai-Feng</creatorcontrib><creatorcontrib>Wu, Li-Zhi</creatorcontrib><creatorcontrib>Tao, Ze-Zhang</creatorcontrib><creatorcontrib>Jiao, Wo-Er</creatorcontrib><creatorcontrib>Chen, Shi-Ming</creatorcontrib><title>Specific knockout of Notch2 in Treg cells significantly inhibits the growth and proliferation of head and neck squamous cell carcinoma in mice</title><title>International immunopharmacology</title><addtitle>Int Immunopharmacol</addtitle><description>•Specific knockout of Notch2 gene in Treg cells can significantly inhibit the growth of HNSCC.•Specific knockout of Notch2 in Treg cells can significantly inhibit the function of Tregs and enhance the anti-HNSCC effect.•The tumor tissues had significant pyroptosis in Treg cell-specific Notch2-knockout mice. To investigate the effect of Notch2 gene knockout in Treg cells on head and neck squamous cell carcinoma (HNSCC) in mice. A mouse model of HNSCC was constructed. Flow cytometry and immunofluorescence were used to examine the numbers of related immune cells and programmed cell death in tumor cells in the spleen and tumor microenvironment of mice. Western blotting was used to measure the expression of related proteins in tumor tissues. The tumor volume of regulatory T (Treg) cell-specific Notch2-knockout mice (experimental group) was significantly smaller than that of control mice (control group) (P &lt; 0.05). Compared with those in the control group, the number of Treg cells and the expression of Ki67 in Treg cells in the spleen and tumor tissue were significantly decreased in the experimental group, while the numbers of CD45+ hematopoietic cells, CD4+ T cells, CD8+ T cells, T helper 1 (Th1) cells, CD11b+ cells (macrophages), and CD11b+CD11c+ cells (dendritic cells) and the expression of Ki67 in CD4+ T cells and CD8+ T cells were significantly increased (P &lt; 0.05). There was no significant difference in the number of Th2 cells between the two groups (P &gt; 0.05). Immunofluorescence analysis showed that the numbers of CD4+ T cells and CD8+ T cells in the tumor tissue in the experimental group were significantly higher than those in the control group (P &lt; 0.05). Compared with that in the control group, programmed cell death in the experimental group was significantly increased (P &lt; 0.05). Moreover, the expression levels of NLRP3, Caspase-1 and GSDMD in the tumor tissues of the experimental group were higher than those in the control group (P &lt; 0.01), while the expression levels of BCL2, Bax, ATG5, LC3 and p62 were not significantly different (P &gt; 0.05). 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To investigate the effect of Notch2 gene knockout in Treg cells on head and neck squamous cell carcinoma (HNSCC) in mice. A mouse model of HNSCC was constructed. Flow cytometry and immunofluorescence were used to examine the numbers of related immune cells and programmed cell death in tumor cells in the spleen and tumor microenvironment of mice. Western blotting was used to measure the expression of related proteins in tumor tissues. The tumor volume of regulatory T (Treg) cell-specific Notch2-knockout mice (experimental group) was significantly smaller than that of control mice (control group) (P &lt; 0.05). Compared with those in the control group, the number of Treg cells and the expression of Ki67 in Treg cells in the spleen and tumor tissue were significantly decreased in the experimental group, while the numbers of CD45+ hematopoietic cells, CD4+ T cells, CD8+ T cells, T helper 1 (Th1) cells, CD11b+ cells (macrophages), and CD11b+CD11c+ cells (dendritic cells) and the expression of Ki67 in CD4+ T cells and CD8+ T cells were significantly increased (P &lt; 0.05). There was no significant difference in the number of Th2 cells between the two groups (P &gt; 0.05). Immunofluorescence analysis showed that the numbers of CD4+ T cells and CD8+ T cells in the tumor tissue in the experimental group were significantly higher than those in the control group (P &lt; 0.05). Compared with that in the control group, programmed cell death in the experimental group was significantly increased (P &lt; 0.05). Moreover, the expression levels of NLRP3, Caspase-1 and GSDMD in the tumor tissues of the experimental group were higher than those in the control group (P &lt; 0.01), while the expression levels of BCL2, Bax, ATG5, LC3 and p62 were not significantly different (P &gt; 0.05). Specific knockout of the Notch2 gene in Treg cells significantly decreases the function of Treg cells, inhibits the growth of HNSCC and improves the immune microenvironment in mice, thus effectively treating HNSCC.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>37523971</pmid><doi>10.1016/j.intimp.2023.110705</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-1216-004X</orcidid></addata></record>
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1878-1705
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subjects Antitumor immunity
Head and neck squamous cell carcinoma
Knockout mice
Notch2
Regulatory T cells
title Specific knockout of Notch2 in Treg cells significantly inhibits the growth and proliferation of head and neck squamous cell carcinoma in mice
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