Tumor Cell-Expressed Herpesvirus Entry Mediator Regulates Proliferation and Adaptive Immunity in Ovarian Cancer

IF 3.1 4区 医学 Q3 IMMUNOLOGY
Yun Lu, Yijun Zhang, Wenxuan Li, Haonan Jiang, Jiapo Wang, Xiaoqing Guo
{"title":"Tumor Cell-Expressed Herpesvirus Entry Mediator Regulates Proliferation and Adaptive Immunity in Ovarian Cancer","authors":"Yun Lu,&nbsp;Yijun Zhang,&nbsp;Wenxuan Li,&nbsp;Haonan Jiang,&nbsp;Jiapo Wang,&nbsp;Xiaoqing Guo","doi":"10.1002/iid3.70175","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Ovarian cancer (OvCa) is a prevalent gynecological malignancy with an increasing incidence and high mortality rate. Although the role of the herpesvirus entry mediator (HVEM), encoded by the <i>TNFRSF14</i> gene, is currently considered pivotal in various types of cancer, the regulation of tumor cell-expressed HVEM in OvCa remains inadequately understood.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Specimens were used to detect HVEM expression via quantitative RT-PCR and flow cytometry. The proliferation of the murine OvCa cell line ID8 was determined using the Cell Counting Kit-8, colony formation, and EdU staining assays. The immune constituents within the ascites fluid and spleen of tumor-bearing mice were analyzed by flow cytometry. Bioinformatics analysis was performed to explore cytokines, chemokines, and signaling pathways regulated by HVEM, and differential expression levels were confirmed via quantitative RT-PCR and western blot analysis.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Herein, we identified a significant upregulation of HVEM in OvCa tissues compared with that in benign tissues and observed dominant expression of HVEM in CD45⁻EpCAM⁺ subsets in OvCa specimens. Tumor cell-expressed HVEM was found to promote OvCa cell proliferation by partly activating spliced X-box-binding protein 1 (XBP1s)-c-Myc signaling. In mouse models, knockdown of <i>Tnfrsf14</i> in ID8 cells alleviated OvCa progression and specifically affected the frequency and function of T cells in the ascites fluid and spleen. In addition, tumor cell-expressed HVEM altered chemokine expression (CXCL1/9/10/11 and CCL2/4/5) and STAT signal activation (STAT5 and STAT6) in ID8 cells.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>This study investigated the effects of HVEM on OvCa and validated its potential as a therapeutic marker for treating OvCa.</p>\n </section>\n </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 3","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70175","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunity, Inflammation and Disease","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/iid3.70175","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background

Ovarian cancer (OvCa) is a prevalent gynecological malignancy with an increasing incidence and high mortality rate. Although the role of the herpesvirus entry mediator (HVEM), encoded by the TNFRSF14 gene, is currently considered pivotal in various types of cancer, the regulation of tumor cell-expressed HVEM in OvCa remains inadequately understood.

Methods

Specimens were used to detect HVEM expression via quantitative RT-PCR and flow cytometry. The proliferation of the murine OvCa cell line ID8 was determined using the Cell Counting Kit-8, colony formation, and EdU staining assays. The immune constituents within the ascites fluid and spleen of tumor-bearing mice were analyzed by flow cytometry. Bioinformatics analysis was performed to explore cytokines, chemokines, and signaling pathways regulated by HVEM, and differential expression levels were confirmed via quantitative RT-PCR and western blot analysis.

Results

Herein, we identified a significant upregulation of HVEM in OvCa tissues compared with that in benign tissues and observed dominant expression of HVEM in CD45⁻EpCAM⁺ subsets in OvCa specimens. Tumor cell-expressed HVEM was found to promote OvCa cell proliferation by partly activating spliced X-box-binding protein 1 (XBP1s)-c-Myc signaling. In mouse models, knockdown of Tnfrsf14 in ID8 cells alleviated OvCa progression and specifically affected the frequency and function of T cells in the ascites fluid and spleen. In addition, tumor cell-expressed HVEM altered chemokine expression (CXCL1/9/10/11 and CCL2/4/5) and STAT signal activation (STAT5 and STAT6) in ID8 cells.

Conclusion

This study investigated the effects of HVEM on OvCa and validated its potential as a therapeutic marker for treating OvCa.

Abstract Image

肿瘤细胞表达的疱疹病毒进入介质调节卵巢癌的增殖和适应性免疫
卵巢癌(OvCa)是一种发病率高、死亡率高的常见妇科恶性肿瘤。尽管由TNFRSF14基因编码的疱疹病毒进入介质(HVEM)目前被认为在各种类型的癌症中起关键作用,但肿瘤细胞表达的HVEM在OvCa中的调控仍未充分了解。方法采用定量RT-PCR和流式细胞术检测HVEM的表达。使用细胞计数试剂盒-8、菌落形成和EdU染色法测定小鼠OvCa细胞系ID8的增殖。用流式细胞术分析荷瘤小鼠腹水和脾脏的免疫成分。通过生物信息学分析,探索HVEM调控的细胞因子、趋化因子和信号通路,并通过定量RT-PCR和western blot分析证实差异表达水平。结果与良性组织相比,我们发现HVEM在OvCa组织中显著上调,并且在OvCa标本中CD45 - EpCAM +亚群中HVEM占优势表达。发现肿瘤细胞表达的HVEM通过部分激活剪接的x- box结合蛋白1 (XBP1s)-c-Myc信号通路促进OvCa细胞增殖。在小鼠模型中,ID8细胞中Tnfrsf14的敲低减轻了OvCa的进展,并特异性地影响了腹水和脾脏中T细胞的频率和功能。此外,肿瘤细胞表达的HVEM改变了ID8细胞的趋化因子表达(CXCL1/9/10/11和CCL2/4/5)和STAT信号激活(STAT5和STAT6)。结论本研究探讨了HVEM对OvCa的影响,并验证了其作为OvCa治疗标志物的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Immunity, Inflammation and Disease
Immunity, Inflammation and Disease Medicine-Immunology and Allergy
CiteScore
3.60
自引率
0.00%
发文量
146
审稿时长
8 weeks
期刊介绍: Immunity, Inflammation and Disease is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research across the broad field of immunology. Immunity, Inflammation and Disease gives rapid consideration to papers in all areas of clinical and basic research. The journal is indexed in Medline and the Science Citation Index Expanded (part of Web of Science), among others. It welcomes original work that enhances the understanding of immunology in areas including: • cellular and molecular immunology • clinical immunology • allergy • immunochemistry • immunogenetics • immune signalling • immune development • imaging • mathematical modelling • autoimmunity • transplantation immunology • cancer immunology
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信