HDAC3 modulates cancer immunity via increasing PD-L1 expression in pancreatic cancer

• Published in: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 2019-03, Vol.19 (2), p.383-389
• Main Authors: Hu, Guofu, He, Nan, Cai, Chuanqi, Cai, Fei, Fan, Ping, Zheng, Zhikun, Jin, Xin
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Apoptosis; Cancer immunity; Cancer therapies; Chemotherapy; Conflicts of interest; Correlation analysis; Gene expression; Histone deacetylase; Histone deacetylase 3 (HDAC3); Immune checkpoint; Immunogenicity; Immunotherapy; Medical prognosis; Pancreatic cancer; Pancreatic ductal adenocarcinoma (PDAC); PD-L1 protein; Plasmids; Programmed death ligand 1 (PD-L1); Proteins; Signal transducer and activator of transcription 3 (STAT3); Stat3 protein; Transcription; Tumor cells; Tumors
• ISSN: 1424-3903; 1424-3911
• DOI: 10.1016/j.pan.2019.01.011

Pancreatic ductal adenocarcinoma (PDAC) is the second leading cause of cancer-related deaths worldwide. Despite immune checkpoints based immunotherapy highlights a new therapeutic strategy and achieves a remarkable therapeutic effect in various types of malignant tumors. Pancreatic cancer is one of the non-immunogenic cancers and is resistant to immunotherapy. Programmed death ligand 1 (PD-L1) is expressed on the surface of tumor cells and its level is a key determinant of the checkpoint immunotherapy efficacy. Here, we reported that the specific inhibitor of histone deacetylase 3 (HDAC3) decreased the protein and mRNA level of PD-L1 in pancreatic cancer cells. Furthermore, we showed that HDAC3 was critical for PD-L1 regulation and positively correlated with PD-L1 in PDAC patient specimens. Finally, we demonstrated that HDAC3/signal transducer and activator of transcription 3 (STAT3) pathway transcriptionally regulated PD-L1 expression. Collectively, our data contributes to a better understanding of the function of HDAC3 in cancer immunity and the regulatory mechanism of PD-L1. More importantly, these data suggest that the HDAC3 inhibitors might be used to improve immunotherapy in pancreatic cancer.