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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2016; 22(2): 748-763
Published online Jan 14, 2016. doi: 10.3748/wjg.v22.i2.748
Viro-immune therapy: A new strategy for treatment of pancreatic cancer
Andrea Marie Ibrahim, Yao-He Wang
Andrea Marie Ibrahim, Yao-He Wang, Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, EC1M6BQ London, United Kingdom
Yao-He Wang, National Centre for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Zhengzhou University, Zhengzhou 450000, Henan Province, China
Author contributions: Wang YH provided the conception of the article; Ibrahim AM and Wang YH designed the article; Ibrahim AM drafted the article while Wang YH made critical revisions related to important intellectual content of the manuscript and approved the final version of the article to be published.
Supported by The United Kingdom Charity Pancreatic Cancer Research Fund, Pancreatic Cancer Research United Kingdom; and Ministry of Sciences and Technology of China, No. 2013DFG32080.
Conflict-of-interest statement: The above-mentioned authors of this manuscript hereby declare that they do not have any conflict-of-interest related to the work submitted herein.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Correspondence to: Yao-He Wang, MD, PhD, Professor of Cancer Cell and Gene Therapy, Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, EC1M6BQ London, United Kingdom. yaohe.wang@qmul.ac.uk
Telephone: +44-20-78823596 Fax: +44-20-78823848
Received: July 29, 2015
Peer-review started: July 30, 2015
First decision: September 29, 2015
Revised: October 26, 2015
Accepted: December 12, 2015
Article in press: December 14, 2015
Published online: January 14, 2016
Processing time: 160 Days and 20.9 Hours
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an almost uniformly lethal disease with less than 5% survival at five years. This is largely due to metastatic disease, which is already present in the majority of patients when diagnosed. Even when the primary cancer can be removed by radical surgery, local recurrence occurs within one year in 50%-80% of cases. Therefore, it is imperative to develop new approaches for the treatment of advanced cancer and the prevention of recurrence after surgery. Tumour-targeted oncolytic viruses (TOVs) have become an attractive therapeutic agent as TOVs can kill cancer cells through multiple mechanisms of action, especially via virus-induced engagement of the immune response specifically against tumour cells. To attack tumour cells effectively, tumour-specific T cells need to overcome negative regulatory signals that suppress their activation or that induce tolerance programmes such as anergy or exhaustion in the tumour microenvironment. In this regard, the recent breakthrough in immunotherapy achieved with immune checkpoint blockade agents, such as anti-cytotoxic T-lymphocyte-associate protein 4, programmed death 1 (PD-1) or PD-L1 antibodies, has demonstrated the possibility of relieving immune suppression in PDAC. Therefore, the combination of oncolytic virotherapy and immune checkpoint blockade agents may synergistically function to enhance the antitumour response, lending the opportunity to be the future for treatment of pancreatic cancer.

Keywords: Anti-cytotoxic T-lymphocyte-associate protein 4; Anti-programmed death receptor ligand 1; Anti-programmed death receptor 1; Immunotherapy; Oncolytic viruses; Pancreatic ductal adenocarcinoma; Pancreatic cancer; Immune checkpoint blockade inhibitors; Cancer vaccine

Core tip: The poor prognosis of pancreatic cancer appeals for a novel strategy to treat this disease. Immunotherapies such as whole cell vaccines are currently being investigated in patients with pancreatic cancer. The recent breakthrough in cancer immunotherapy with immune checkpoint inhibitors has allowed us to reverse T cell anergy and enhance antitumour immunity. Tumour-targeted Oncolytic viruses in combination with checkpoint inhibitors function synergistically to increase the tumour antigen load, relieve immune suppression in the tumour bed while enhancing the activation of the adaptive immune system. Viro-immune-checkpoint therapy should thus be considered as a novel strategy to treat pancreatic cancer.