Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Sep 15, 2018; 10(9): 221-227
Published online Sep 15, 2018. doi: 10.4251/wjgo.v10.i9.221
Immune blockade inhibitors and the radiation abscopal effect in gastrointestinal cancers
Ioannis A Voutsadakis
Ioannis A Voutsadakis, Algoma District Cancer Program, Sault Area Hospital, Sault Ste. Marie, ON P6B 0A8, Canada
Ioannis A Voutsadakis, Section of Internal Medicine, Division of Clinical Sciences, Northern Ontario School of Medicine, Sudbury, ON P3E 2C6, Canada
Author contributions: Voutsadakis IA is the sole contributor in this manuscript.
Conflict-of-interest statement: The author has no conflicts of interest regarding this paper.
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: Ioannis A Voutsadakis, MD, PhD, Doctor, Algoma District Cancer Program, Sault Area Hospital, 750 Great Northern Road, Sault Ste. Marie, ON P6B 0A8, Canada. ivoutsadakis@yahoo.com
Telephone: +1-705-7593434 Fax: +1-705-7593815
Received: July 17, 2018
Peer-review started: July 17, 2018
First decision: August 8, 2018
Revised: August 13, 2018
Accepted: August 27, 2018
Article in press: August 28, 2018
Published online: September 15, 2018

The field of tumor immunology has produced in the recent years a revolution in cancer therapeutics putting an end in the long lasting frustration of investigators in the area stemming from largely unsuccessful strides to develop cancer vaccines. This progress has come from the introduction of immune checkpoint inhibitors, monoclonal antibodies blocking ligand/receptor pairs with inhibitory effects for immune cells. Through this blockade immune checkpoint blockers are able to activate the immune system and create an anti-tumoral effect. A significant sub-set of patients with various types of cancers such as melanoma, lung carcinomas and urothelial cancers benefit from treatment with these drugs and survivals have improved in some cases. However other cancers are primarily resistant to immune blockers and secondary resistance is also the norm. Radiation therapy is often used in the palliative treatment of patients with advanced cancers and, in addition to the local effect in the irradiated field, it may in rare cases produce a systemic antitumor effect, termed “abscopal”. This effect has been suggested to be produced by immune mechanisms. Thus an opportunity presents for a synergistic effect of immune stimulation between radiation and immune blockade inhibitors. The therapeutic opportunities presented with the combination of radiation and these drugs for gastrointestinal cancers will be discussed in this editorial overview.

Keywords: Abscopal effect, Radiation, CD28/cytotoxic T-lymphocyte antigen-4, Immune blockade inhibitors, Programmed death 1, Programmed death ligand-1

Core tip: Immune checkpoint inhibitors activate the immune response to tumors by blocking inhibitory receptor pairs. Radiation treatment may also promote anti-tumor immune response. Thus, there exist an opportunity for synergy between the two treatment modalities that may be exploited therapeutically in gastrointestinal and other cancers.