Abstract
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.
Original language | English |
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Article number | 3219 |
Journal | Cancers |
Volume | 16 |
Issue number | 18 |
DOIs | |
State | Published - Sep 2024 |
Keywords
- Epstein–Barr virus
- MICA
- NF-κB
- androgen receptor
- dihydrotestosterone