PD-L1 combined with HDAC9 is a useful prognostic predictor in hepatocellular carcinoma

BACKGROUND: The expression of programmed death-ligand 1 (PD-L1) is associated with the response of patients to PD-1/PD-L1 blockade immunotherapy. It has been demonstrated that histone deacetylase (HDAC) inhibitors may alter the expression of PD-L1/PD-L2 and enhance the antitumor immune responses. However, the profile of PD-L1 expression and its association with HDACs in hepatocellular carcinoma (HCC) has not been accurately investigated. METHODS: The expression of PD-L1 and HDACs were examined by immunohistochemical (IHC) staining using tissue microarray (TMA) of 109 HCC specimens. Expression data from TCGA database and IHC staining of TMA were used for correlation analysis. Survival rates were analyzed based on data from 109 HCC patients. RESULTS: We found that PD-L1 was upregulated in the majority of HCC samples. Furthermore, correlation analysis revealed that PD-L1 expression was positively correlated with HDAC9 and HDAC2 expression in HCC. Survival analysis showed that high levels of PD-L1 combined with increased expression of HDAC9 decreased overall survival (OS) in patients with HCC. In addition, univariate and multivariate analysis further suggested that the increased PD-L1/HDAC9 expression was an independent prognostic biomarker in HCC. HDAC9 overexpression promoted HCC growth and PD-L1 expression. CONCLUSIONS: The results of the current study highlighted the strong association between HDACs with immunotherapy, thus providing a rational basis for combining HDAC9 specific inhibitors and PD-1 blockade in a future clinical approach for HCC.