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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2019

Open Access 01-12-2019 | Pancreatic Cancer | Research

Overexpressed histone acetyltransferase 1 regulates cancer immunity by increasing programmed death-ligand 1 expression in pancreatic cancer

Authors: Ping Fan, Jingyuan Zhao, Zibo Meng, Heyu Wu, Bo Wang, Heshui Wu, Xin Jin

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2019

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Abstracts

Background

Pancreatic ductal adenocarcinoma is one of the leading causes of cancer-related death worldwide. Immune checkpoint blockade therapy, including anti-PD-1 and anti-PD-L1, is a new therapeutic strategy for cancer treatment but the monotherapy with PD-L1 inhibitors for pancreatic cancer is almost ineffective for pancreatic cancer. Thus, exploring the regulatory mechanism of PD-L1 in cancer cells, especially in pancreatic cancer cells, is one of the key strategies to improving cancer patient response to PD-L1 blockade therapy. Histone acetyltransferase 1(HAT1) is a classic type B histone acetyltransferase and the biological role of HAT1 in pancreatic cancer is unclear.

Methods

The clinical relevance of HAT1 was examined by the GEPIA web tool, Western blotting and immunohistochemistry of pancreatic cancer tissue microarray slides. Tumor cell motility was investigated by MTS assay, colony formation assay and xenografts. The relationship between HAT1 and PD-L1 was examined by Western blot analysis, RT-qPCR and immunohistochemistry.

Results

HAT1 was upregulated in PDAC and associated with poor prognosis in PDAC patients. The knockdown of HAT1 decreased the proliferation of pancreatic cancer cells in vivo and in vitro. Strikingly, we showed that HAT1 transcriptionally regulated PD-L1, and this process was mainly mediated by BRD4 in pancreatic cancer. The knockdown of HAT1 improved the efficacy of immune checkpoint blockade by decreasing the PD-L1.

Conclusions

The recognition of HAT1 in regulating tumor cell proliferation and cancer immunity indicated that HAT1 might be employed as a new diagnostic and prognostic marker and a predictive marker for pancreatic cancer therapy, especially in immune checkpoint blockade therapy. Targeting HAT1 highlights a novel therapeutic approach to overcome immune evasion by tumor cells.
Appendix
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Metadata
Title
Overexpressed histone acetyltransferase 1 regulates cancer immunity by increasing programmed death-ligand 1 expression in pancreatic cancer
Authors
Ping Fan
Jingyuan Zhao
Zibo Meng
Heyu Wu
Bo Wang
Heshui Wu
Xin Jin
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2019
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-019-1044-z

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