Research ArticleCancer

A selective HDAC8 inhibitor potentiates antitumor immunity and efficacy of immune checkpoint blockade in hepatocellular carcinoma

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Science Translational Medicine  07 Apr 2021:
Vol. 13, Issue 588, eaaz6804
DOI: 10.1126/scitranslmed.aaz6804

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Enhancing through epigenetics

A challenge for cancer immunotherapy is the need to turn cold, immune cell–excluded tumors into hot, inflamed tumors. Here, Yang et al. investigated the role of histone deacetylase 8 (HDAC8) in maintaining immune cell–excluded tumors. The authors showed that selective pharmacological inhibition of HDAC8 changed the epigenetic landscape of hepatocellular carcinoma cells, leading to production of T cell–recruiting chemokines. Treatment of hepatocellular carcinoma–bearing mice with the selective HDAC8 inhibitor resulted in increased infiltration of CD8+ T cells. Further, treatment with the HDAC8 inhibitor and immune checkpoint blockade led to enhanced control of tumors with no evidence of toxicity. Thus, epigenetic reprogramming used in combination with immunotherapy may be a promising approach for treating hepatocellular carcinomas and other immunologically cold tumors.

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