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

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...

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Bibliographic Details
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
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Summary: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.
ISSN:1424-3903
1424-3911
DOI:10.1016/j.pan.2019.01.011