https://scholars.lib.ntu.edu.tw/handle/123456789/638452
標題: | Metastasis and immunosuppression promoted by mtDNA and PD-L1 in extracellular vesicles are reversed by WGP β-glucan in oral squamous cell carcinoma | 作者: | HUI-HSIN KO Peng, Hsin Hui Cheng, An Ning HAN-YI E. CHOU HSIN-HAN HOU WEI-TING KUO WEI-WEN LIU YEN-PING KUO Lee, Alan Yueh Luen SHIH-JUNG CHENG |
關鍵字: | extracellular vesicle | mitochondrial DNA D-loop | oral squamous cell carcinoma | programmed cell death-ligand 1 | whole glucan particle β-glucan | 公開日期: | 1-十月-2023 | 卷: | 114 | 期: | 10 | 來源出版物: | Cancer Science | 摘要: | The suppressive regulatory T cells (Treg) are frequently upregulated in cancer patients. This study aims to demonstrate the hypothesis that arecoline could induce the secretion of mitochondrial (mt) DNA D-loop and programmed cell death-ligand 1 (PD-L1) in extracellular vesicles (EVs), and attenuate T-cell immunity by upregulated Treg cell numbers. However, the immunosuppression could be reversed by whole glucan particle (WGP) β-glucan in oral squamous cell (OSCC) patients. Arecoline-induced reactive oxygen specimen (ROS) production and cytosolic mtDNA D-loop were analyzed in OSCC cell lines. mtDNA D-loop, PD-L1, IFN-γ, and Treg cells were also identified for the surgical specimens and sera of 60 OSCC patients. We demonstrated that higher mtDNA D-loop, PD-L1, and Treg cell numbers were significantly correlated with larger tumor size, nodal metastasis, advanced clinical stage, and areca quid chewing. Furthermore, multivariate analysis confirmed that higher mtDNA D-loop levels and Treg cell numbers were unfavorable independent factors for survival. Arecoline significantly induced cytosolic mtDNA D-loop leakage and PD-L1 expression, which were packaged by EVs to promote immunosuppressive Treg cell numbers. However, WGP β-glucan could elevate CD4+ and CD8+ T-cell numbers, mitigate Treg cell numbers, and promote oral cancer cell apoptosis. To sum up, arecoline induces EV production carrying mtDNA D-loop and PD-L1, and in turn elicits immune suppression. However, WGP β-glucan potentially enhances dual effects on T-cell immunity and cell apoptosis and we highly recommend its integration with targeted and immune therapies against OSCC. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/638452 | ISSN: | 13479032 | DOI: | 10.1111/cas.15919 |
顯示於: | 口腔生物科學研究所 |
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