Enhancing the efficacy of liver cancer immunotherapy by specific inhibition of histone deacetylase 8
Refereed conference paper presented and published in conference proceedings


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摘要Accumulating evidence is underscoring the fundamental importance of epigenetic regulation in tumor immune evasion. We have previously elucidated a critical role of histone deacetylase 8 (HDAC8) in hepatic carcinogenesis. Here, we aim to investigate the therapeutic potential of a HDAC8-specific inhibitor PCI-34051 in preclinical hepatocellular carcinoma (HCC) models. PCI-34051 significantly reduced HCC tumorigenicity in immunocompetent but not immunodeficient mice. Immune profiling revealed specific reduction in tumor-infiltrating regulatory T cells, which was associated with significant increase in CD8+ T cells. Notably, combined PCI-34051 and anti-PD-L1 treatment resulted in complete tumor eradication in all of the co-treated mice. Moreover, the combination therapy promoted long-term survival, which was associated with elevated CD8+ T effector and central memory cells. Our data suggest that selective chromatin modifications by HDAC8 alter the tumor immune surveillance program and demonstrate the potential of rational combinatorial epigenetic immunotherapy to fully unleash T-cell responses, leading to long-term remission of HCC.
著者Weiqin YANG, Jingying ZHOU, Yu FENG, Hangyong SUN, Stephen L CHAN, Anthony W.H. CHAN, Zhiwei CHEN, Ka-Fai TO, Alfred Sze-Lok CHENG
會議名稱The 77th Annual Meeting of the Japanese Cancer Association
會議開始日27.09.2018
會議完結日29.09.2018
會議地點Osaka
會議國家/地區日本
會議論文集題名Cancer Science
出版年份2018
月份12
卷號109
期次Suppl 2
出版社Wiley
頁次206 - 206
國際標準期刊號1349-7006
語言英式英語

上次更新時間 2020-05-08 於 06:03