Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2020; 26(26): 3737-3749
Published online Jul 14, 2020. doi: 10.3748/wjg.v26.i26.3737
Combining protein arginine methyltransferase inhibitor and anti-programmed death-ligand-1 inhibits pancreatic cancer progression
Nan-Nan Zheng, Min Zhou, Fang Sun, Man-Xiu Huai, Yi Zhang, Chun-Ying Qu, Feng Shen, Lei-Ming Xu
Nan-Nan Zheng, Min Zhou, Fang Sun, Man-Xiu Huai, Yi Zhang, Chun-Ying Qu, Feng Shen, Lei-Ming Xu, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Author contributions: Zheng NN and Zhou M contributed equally to this work; Zheng NN and Zhou M performed the majority of the experiments and wrote the paper; Sun F and Huai MX analyzed the data; Zhang Y, Qu CY, and Shen F edited the manuscript; Xu LM designed and supervised the study; all authors have read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 81472844.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine.
Institutional animal care and use committee statement: This study was reviewed and approved by the Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (XHEC-F- 2018-062).
Conflict-of-interest statement: The authors declare that there are no conflicts of interest related to this study.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Lei-Ming Xu, MD, PhD, Chief Doctor, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665, Kongjiang Road, Yangpu District, Shanghai 200092, China. xuleiming@xinhuamed.com.cn
Received: January 19, 2020
Peer-review started: January 19, 2020
First decision: May 1, 2019
Revised: June 2, 2020
Accepted: June 20, 2020
Article in press: June 20, 2020
Published online: July 14, 2020
Core Tip

Core tip: Pancreatic ductal adenocarcinoma exhibits marginal responses to immune checkpoint inhibitors targeting programmed death-ligand-1 (PD-L1), and the underlying mechanism remains poorly understood. PT1001B, an inhibitor of type I protein arginine methyltransferases (PRMTs), significantly enhanced the therapeutic efficacy of anti-PD-L1 mAb. PT1001B improved antitumor immunity by inhibiting PD-L1 expression on tumor cells, upregulating tumor infiltrating CD8+ T lymphocytes, and decreasing PD-1+ leukocytes. In addition, PT1001B amplified the inhibitory effect of anti-PD-L1 on tumor cell proliferation and enhanced the induction of tumor cell apoptosis. PRMT1 downregulation was correlated with PD-L1 downregulation. Thus, PRMT1 is a potential therapeutic target.