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


摘要Hepatocellular carcinoma, as the worldwide fifth leading cancer, has exerted great threats to human health. Immune checkpoint therapies that targeting co-inhibitory molecules like programmed death 1 (PD-1)/PD-ligand 1 (L1) axis exhibited notable anti-tumor effect in various cancer types via enhancing cytotoxicity T lymphocytes (CTL). Unfortunately, responding rate of PD-1/PD-L1-based immunotherapy remains lower than 20% due to lack of CTL infiltration in tumor mass in HCC. We have previously unfolded the oncogenic role of HDAC8 in hepatocellular carcinogenesis, while the detailed immunoregulatory function of HDAC8 has not been studied yet.
Here, we report that HDAC8 inhibition drove remarkable enhancement on tumor CTL infiltration in a chemokine-dependent manner in an orthotopic mouse HCC model. Interestingly, the inhibition of HDAC8 also significantly reduced regulatory T (Treg) cells proportion and ameliorated the suppressive tumor microenvironment. Above all, HDAC8 inhibition hereby substantially improved the efficacy of PD-1/PD-L1 axis blockade to eradicate large hepatoma and extended the surviving period for more than one year with no recurrence observed. Furthermore, we observed that combinatorial treatment further developed potent T cell memory in circulatory system, which protected cured mice from re-challenge of the same HCC cell line. By improving the efficacy of anti-PD-L1 treatment in mouse model, our study further shed lights on how to develop a combinatorial therapy in clinical trial.
著者Yu FENG, Weiqin YANG, Jingying ZHOU, Ka Wing Otto CHEUNG, Zhiwei CHEN, Kevin YIP, Ka-Fai TO, Alfred CHENG
會議名稱The Cold Spring Harbor Asia on Scientific and Technical Advances in Cancer Immunology
關鍵詞tumor microenvironment, combinatorial therapy, hepatocellular carcinoma, PD-1/PD-L1, HDAC8

上次更新時間 2019-02-12 於 15:45