Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2016; 22(33): 7440-7452
Published online Sep 7, 2016. doi: 10.3748/wjg.v22.i33.7440
Immune checkpoint and inflammation as therapeutic targets in pancreatic carcinoma
Shiro Kimbara, Shunsuke Kondo
Shiro Kimbara, Shunsuke Kondo, Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo 104-0045, Japan
Author contributions: Kimbara S and Kondo S contributed equally to this work.
Supported by JSPS Grant-in-Aid for Young Scientists (B), No. 268605371; AstraZeneca, Eli Lilly and Company, and Bayer AG (to Kondo S).
Conflict-of-interest statement: Shiro Kimbara have no conflict of interest associated with this manuscript. Shunsuke Kondo received research funding from AstraZeneca, Eli Lilly and Company, and Bayer AG.
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:
Correspondence to: Shunsuke Kondo, MD, PhD, Department of Experimental Therapeutics, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Telephone: +81-3-35422511 Fax: +81-3-35423815
Received: March 26, 2016
Peer-review started: March 27, 2016
First decision: May 12, 2016
Revised: June 30, 2016
Accepted: August 1, 2016
Article in press: August 1, 2016
Published online: September 7, 2016

Pancreatic adenocarcinoma (PAC) is one of the most deadly malignant neoplasms, and the efficacy of conventional cytotoxic chemotherapy is far from satisfactory. Recent research studies have revealed that immunosuppression and inflammation are associated with oncogenesis, as well as tumor development, invasion, and metastasis in PAC. Thus, immunosuppression-related signaling, especially that involving immune checkpoint and inflammation, has emerged as novel treatment targets for PAC. However, PAC is an immune-resistant tumor, and it is still unclear whether immune checkpoint or anti-inflammation therapies would be an ideal strategy. In this article, we will review immune checkpoint and inflammation as potential targets, as well as clinical trials and the prospects for immunotherapy in PAC.

Keywords: Immune checkpoint, Therapeutic anticancer target, Inflammation, Randomized clinical trial, Pancreatic adenocarcinoma

Core tip: Pancreatic adenocarcinoma is recognized as one of the most malignant neoplasms, and more efficacious treatment is desired earnestly. Recent research studies have revealed that the development and progression of pancreatic adenocarcinoma are highly influenced by immune responses, and inflammation is a critical promoter of the disease. In this article, we highlighted the emergence of immunosuppression-related signaling associated with immune checkpoint and inflammation, as a novel treatment target for cancer. Furthermore, the review demonstrated that the current focus on therapeutic strategies involving combination chemotherapy, immunotherapy, and anti-inflammation therapy might provide considerably more clinical benefits to patients than current therapies.