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
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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.

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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
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