Background: Epstein–Barr virus-associated gastric carcinoma (EBVaGC) is a subset of gastric cancers linked to EBV infection. While the role of male hormones in cancers such as prostate, breast, and ovarian cancers is well-studied, their impact on EBVaGC remains less understood. This study aims to examine the effect of dihydrotestosterone (DHT) on EBVaGC, particularly focusing on its influence on the immune response. Methods: The study utilized the SNU719 EBVaGC cell line. Cells were treated with DHT to assess androgen receptor (AR) expression and the activation of signaling pathways, including NF-κB. The expression of MHC class I polypeptide-related sequence A (MICA) and its interaction with the NKG2D receptor on NK and T cells was evaluated. Cytotoxicity assays were conducted to determine DHT’s effect on NK and T cell-mediated cytotoxicity, and proinflammatory cytokine gene expression was analyzed. Results: DHT significantly increased AR expression in EBVaGC cells and activated the NF-κB pathway, which led to increased transcription of target genes such as MICA and EBNA1. These changes enhanced the interaction with receptors on NK and T cells, thereby boosting their cytotoxicity against EBVaGC cells. Importantly, DHT did not upregulate proinflammatory cytokine genes. Conclusion: DHT enhances the immune response against EBVaGC by upregulating MICA and activating NK and T cells. These findings suggest potential therapeutic strategies targeting androgen signaling to improve anti-tumor immunity in EBVaGC.
背景：Epstein-Barr病毒相关胃癌（EBVaGC）是与EBV感染相关的胃癌亚型。虽然雄激素在前列腺癌、乳腺癌和卵巢癌等癌症中的作用已有深入研究，但其对EBVaGC的影响尚不明确。本研究旨在探讨二氢睾酮（DHT）对EBVaGC的作用，重点关注其对免疫应答的影响。 方法：研究采用SNU719 EBVaGC细胞系。通过DHT处理细胞，评估雄激素受体（AR）表达及NF-κB等信号通路的激活情况。检测MHC I类多肽相关序列A（MICA）的表达及其与NK和T细胞表面NKG2D受体的相互作用。通过细胞毒性实验分析DHT对NK和T细胞介导的细胞毒性的影响，并检测促炎细胞因子基因表达。 结果：DHT显著提升EBVaGC细胞中AR表达，并激活NF-κB通路，进而促进MICA和EBNA1等靶基因的转录。这些变化增强了与NK和T细胞受体的相互作用，从而提升其对EBVaGC细胞的细胞毒性。值得注意的是，DHT并未上调促炎细胞因子基因表达。 结论：DHT通过上调MICA表达并激活NK和T细胞，增强针对EBVaGC的免疫应答。这些发现提示靶向雄激素信号通路可能成为改善EBVaGC抗肿瘤免疫的潜在治疗策略。
肿瘤(癌症)患者之家