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World J Meta-Anal. Mar 31, 2019; 7(3): 101-109
Published online Mar 31, 2019. doi: 10.13105/wjma.v7.i3.101
PD-1/PD-L1 antagonists in gastric cancer: Current studies and perspectives
Jian Li, Xiao-Hong Zhang, Song-Hua Bei, Li Feng
Jian Li, Xiao-Hong Zhang, Song-Hua Bei, Li Feng, Endoscopy Center, Minhang Branch of Zhongshan Hospital, Fudan University, Shanghai 201100, China
Author contributions: Feng L conceived this topic and organized the manuscript; Li J wrote the first draft of the manuscript; Zhang XH and Bei SH contributed to manuscript revision; all authors have read and approved the submitted version and are accountable for all aspects of the work.
Supported by Minhang District University Building Project, No. 2017MWDXK03.
Conflict-of-interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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/
Corresponding author: Li Feng, MD, Chief Doctor, Endoscopy Center, Minhang Branch of Zhongshan Hospital, Fudan University, No. 170, Xinsong Road, Minhang District, Shanghai 201100, China. 13247793069@163.com
Telephone: +86-21-64923400-6307 Fax: +86-21-64923400-6307
Received: February 18, 2019
Peer-review started: February 18, 2019
First decision: March 20, 2019
Revised: March 26, 2019
Accepted: March 26, 2019
Article in press: March 27, 2019
Published online: March 31, 2019
Processing time: 42 Days and 1 Hours
Abstract

Immune checkpoints release suppressive signals for T cells, which enable the tumors to escape from immune destruction and provide a new concept that uses the capabilities of the immune system as a therapeutic target for tumors. At present, programmed death receptor 1 (PD-1)/programmed death ligand-1 (PD-L1) has become the most promising therapeutic target. PD-1/PD-L1 blockades exhibit long-lasting antitumor efficacy and safety in patients with various cancers, such as melanoma and non-small-cell lung cancer. Moreover, PD-L1 is highly expressed in the peripheral blood and tumor specimens of patients with cancer, and the expression of PD-L1 is positively correlated with various pathological features and may serve as a predictor of poor prognosis or a diagnostic tool. Clinical trials have verified that PD-1/PD-L1 blockade therapy benefits patients with advanced gastric cancer or gastroesophageal junction cancer. Furthermore, there are many molecules involved in the regulation of PD-1/PD-L1 expression, and the modification of these molecules via drugs and combinations with PD-1/PD-L1 inhibitors may further improve the efficacy of immunotherapy for gastric cancer. In this review, the efficacy, safety, and possible combination treatment options of PD-1/PD-L1 in gastric cancer are reviewed in experimental and clinical settings.

Keywords: Immunotherapy; PD-1/PD-L1 inhibitors; Programmed death-ligand 1; Gastric cancer

Core tip: Programmed death receptor 1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors have been defined as a distinct type of immunotherapy for various cancers. A growing number of studies have investigated the role of PD-1/PD-L1 inhibitors in gastric cancer. This manuscript presents a comprehensive overview of the mechanism of PD-1/PD-L1 blockade therapy, summarizes the efficacy and safety of some critical clinical trials, and highlights possible combination treatment options in gastric cancer. This manuscript also provides insight into the current research limitations and indicates the development direction for future research of PD-1/PD-L1 checkpoint inhibitors.