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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AbstractAccumulating 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.
All Author(s) ListWeiqin YANG, Jingying ZHOU, Yu FENG, Hangyong SUN, Stephen L CHAN, Anthony W.H. CHAN, Zhiwei CHEN, Ka-Fai TO, Alfred Sze-Lok CHENG
Name of ConferenceThe 77th Annual Meeting of the Japanese Cancer Association
Start Date of Conference27/09/2018
End Date of Conference29/09/2018
Place of ConferenceOsaka
Country/Region of ConferenceJapan
Proceedings TitleCancer Science
Year2018
Month12
Volume Number109
Issue NumberSuppl 2
PublisherWiley
Pages206 - 206
ISSN1349-7006
LanguagesEnglish-United Kingdom

Last updated on 2020-04-07 at 04:24