Editorial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Aug 15, 2015; 7(8): 95-101
Published online Aug 15, 2015. doi: 10.4251/wjgo.v7.i8.95
Anti program death-1/anti program death-ligand 1 in digestive cancers
Eléonore de Guillebon, Pauline Roussille, Eric Frouin, David Tougeron
Eléonore de Guillebon, David Tougeron, Medical Oncology Department, Poitiers University Hospital, 86000 Poitiers, France
Pauline Roussille, Radiation Oncology Department, Poitiers University Hospital, 86000 Poitiers, France
Eric Frouin, Pathology Department, Poitiers University Hospital, 86000 Poitiers, France
Eric Frouin, David Tougeron, Laboratory Inflammation, Tissus Epithéliaux et Cytokines, EA 4331, Poitiers University, 86000 Poitiers, France
David Tougeron, Gastroenterology Department, Poitiers University Hospital, 86000 Poitiers, France
Author contributions: de Guillebon E, Roussille P, Frouin E and Tougeron D contributed to conception and design of the paper; de Guillebon E and Tougeron D contributed to analysis and interpretation of literature data and drafting of the manuscript; de Guillebon E, Roussille P, Frouin E and Tougeron D contributed to critical revisions of the manuscript; de Guillebon E, Roussille P, Frouin E and Tougeron D contributed to final approval of the article.
Conflict-of-interest statement: Eléonore de Guillebon, Pauline Roussille, Eric Frouin have no conflict of interest; David Tougeron is a principal investigator for a Roche study with an anti PD-L1 monoclonal antibody.
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: David Tougeron, MD, PhD, Gastroenterology Department, Poitiers University Hospital, 2 rue de la Milétrie, 86000 Poitiers, France. david.tougeron@chu-poitiers.fr
Telephone: +33-5-49443751 Fax: +33-5-49443835
Received: February 14, 2015
Peer-review started: February 22, 2015
First decision: March 20, 2015
Revised: May 12, 2015
Accepted: May 27, 2015
Article in press: May 28, 2015
Published online: August 15, 2015
Processing time: 181 Days and 17.3 Hours
Abstract

Human tumors tend to activate the immune system regulatory checkpoints as a means of escaping immunosurveillance. For instance, interaction between program

death-1 (PD-1) and program death-ligand 1 (PD-L1) will

lead the activated T cell to a state of anergy. PD-L1 is upregulated on a wide range of cancer cells. Anti-PD-1 and anti-PD-L1 monoclonal antibodies (mAbs), called immune checkpoint inhibitors (ICIs), have consequently been designed to restore T cell activity. Accumulating data are in favor of an association between PD-L1 expression in tumors and response to treatment. A PD-L1 expression is present in 30% to 50% of digestive cancers. Multiple anti-PD-1 (nivolumab, pembrolizumab) and anti-PD-L1 mAbs (MPDL3280A, Medi4736) are under evaluation in digestive cancers. Preliminary results in metastatic gastric cancer with pembrolizumab are highly promising and phase II will start soon. In metastatic colorectal cancer (CRC), a phase III trial of MPDL3280A as maintenance therapy will shortly be initiated. Trials are also ongoing in metastatic CRC with high immune T cell infiltration (i.e., microsatellite instability). Major challenges are ahead in order to determine how, when and for which patients we should use these ICIs. New radiologic criteria to evaluate tumor response to ICIs are awaiting prospective validation. The optimal therapeutic sequence and association with cytotoxic chemotherapy needs to be established. Finally, biomarker identification will be crucial to selection of patients likely to benefit from ICIs.

Keywords: Program death-1; Program death-ligand 1; Antibody; Digestive cancer

Core tip: Anti-program death-1 and anti-program death-ligand 1 (PD-L1) monoclonal antibodies have been designed to restore T cell activity, since human tumors tend to activate this immune regulatory checkpoint as a means of escaping immunosurveillance. A PD-L1 expression is present in 30% to 50% of digestive cancers and accumulating data are in favor of an association between this PD-L1 expression and response to treatment, which make digestive cancers promising candidates for those breakthrough immunotherapies. We review the ongoing clinical trials and the major challenges ahead of us in order to learn how, when and for which patients we should use these therapeutics.