CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
脱氢表雄酮通过 NF-κB p65/miR-15b-5p/B7-H4 轴减弱口腔鳞状细胞癌的免疫逃逸
英文原题：Dehydroepiandrosterone attenuated the immune escape of oral squamous cell carcinoma through NF-κB p65/miR-15b-5p/B7-H4 axis.
查看英文原题
Dehydroepiandrosterone attenuated the immune escape of oral squamous cell carcinoma through NF-κB p65/miR-15b-5p/B7-H4 axis.
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研究概要
本研究表明，DHEA 通过抑制 B7-H4 表达减弱口腔鳞状细胞癌细胞的免疫逃逸，为癌症免疫治疗提供了新的见解。
中文摘要
本研究旨在探讨脱氢表雄酮（DHEA）对口腔鳞状细胞癌（OSCC）免疫逃逸的影响及作用机制，为增强免疫疗法效果提供依据。
采用异种移植小鼠模型和免疫组织化学揭示TIL（肿瘤浸润淋巴细胞）分布模式。体外研究使用 CAL27 和 SCC VII 细胞系。采用蛋白质印迹、qPCR、免疫荧光和流式细胞术评估 B7-H4 表达。使用重组小鼠 B7-H4 蛋白（rmB7-H4）和 NF-κB p65 抑制剂 PG490 开展“挽救实验”。通过功能获得与功能缺失、荧光素酶报告及染色质免疫沉淀实验验证相关机制。
DHEA 抑制 OSCC 异种移植小鼠模型肿瘤生长，增加 TIL 中 CD8+ 细胞并减少 FOXP3+ 细胞。DHEA 降低 CAL27 和 SCC VII 细胞中的 B7-H4 表达；rmB7-H4 可逆转 DHEA 对肿瘤生长和 TIL 分布的作用。DHEA 增加 miR-15b-5p 表达并激活其转录因子 NF-κB p65。进一步实验表明，miR-15b-5p 可通过结合 B7-H4 的 3′ 非翻译区抑制其表达，而 NF-κB p65 可激活 miR-15b 转录。PG490 可逆转 DHEA 对 OSCC 异种移植模型肿瘤生长和抗肿瘤免疫的影响，以及对 NF-κB p65、miR-15b-5p 和 B7-H4 表达/磷酸化的作用。
本研究表明，DHEA 通过抑制 B7-H4 表达减轻 OSCC 细胞免疫逃逸，为癌症免疫疗法提供了新见解。
展开英文摘要原文
We aimed to explore the effects and mechanisms of action of dehydroepiandrosterone (DHEA) on immune evasion of oral squamous cell carcinoma (OSCC) to provide evidence for enhancing the effect of immunotherapy.
A xenograft mouse model and immunohistochemistry were used to reveal the patterns of tumor-infiltrating lymphocytes (TILs). The CAL27 and SCC VII cell lines were used for the in vitro study. Western blotting, qPCR, immunofluorescence, and flow cytometry were used to evaluate the expression of B7-H4. Recombinant mouse B7-H4 protein (rmB7-H4) and PG490, an inhibitor of NF- B p65 were used for the "rescue study." Gain- and loss-of-function, luciferase reporter, and chromatin immunoprecipitation assays were performed to verify this mechanism.
DHEA inhibited tumor growth in an OSCC xenograft mouse model, increased CD8 + cells, and decreased FOXP3 + cells in TILs. DHEA reduced the expression of B7-H4 in CAL27 and SCC VII cells RmB7-H4 reverses the effect of DHEA on tumor growth and TIL patterns. DHEA increased the expression of miR-15b-5p and activated its transcriptional factor NF- B p65. Further experiments demonstrated that miR-15b-5p inhibited B7-H4 expression by binding to its 3'-UTR regions, and NF- B p65 activated miR-15b transcription. PG490 reversed the effects of DHEA on tumor growth, antitumor immunity in the OSCC xenograft model, and the expression/phosphorylation of NF- B p65, miR-15b-5p, and B7-H4.
This study indicates that DHEA attenuates the immune escape of OSCC cells by inhibiting B7-H4 expression, providing new insights for cancer immunotherapy.
论文信息
- 作者
- Wang Y、Li R、Yuan R、Wang L、Qiao Q、Han Z、Li Q、Li Y
- 第一作者单位
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, No. 22, Zhongguancun South Avenue, Haidian District, Beijing 100081, PR China. Electronic address: wyf_pkuss@126.com.China
- 通讯作者单位
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, No. 22, Zhongguancun South Avenue, Haidian District, Beijing 100081, PR China. Electronic address: guodazuo@sina.com.China
- 期刊
- International immunopharmacology2024 Aug 20
- 原文标识
- PubMed 38885603 · DOI 10.1016/j.intimp.2024.112480