Editorial
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Immunol. Dec 21, 2018; 8(1): 1-11
Published online Dec 21, 2018. doi: 10.5411/wji.v8.i1.1
Cancer immunotherapy by targeting immune checkpoint receptors
Noah Isakov
Noah Isakov, Department of Microbiology, Immunology and Genetics, Ben-Gurion University, Beer Sheva 84105, Israel
Author contributions: Isakov N performed all activities for preparation of this manuscript.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
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 to: Noah Isakov, PhD, Professor, Department of Microbiology, Immunology and Genetics, Ben-Gurion University, POB. 653, Beer Sheva 84105, Israel. noah@bgu.ac.il
Telephone: +972-8-6477267 Fax: +972-8-6477626
Received: August 30, 2018
Peer-review started: August 30, 2018
First decision: October 22, 2018
Revised: November 10, 2018
Accepted: November 29, 2018
Article in press: November 29, 2018
Published online: December 21, 2018
Abstract

The immune system plays a pivotal role in defending our body from invading pathogens and in surveillance against cancer. While most cells that acquire mutations are detected and destroyed by immunocytes, a small number of transformed cells succeed in evading immune destruction by inhibiting immune checkpoint regulatory pathways, leading to suppression of anti-cancer immune responses. Under normal conditions, immune checkpoint receptors maintain self-tolerance, prevent immunopathology, and regulate overall immune homeostasis. However, their skewed activation by cancer cells may lead to the suppression of nascent anti-tumor immunity and the promotion of tumor growth. Discovering the role of immune checkpoints in cancer and understanding their mode of operation has led to the development of novel strategies for cancer immunotherapy, which are based on the intervention or blockade of immune checkpoint-regulated pathways. Clinical studies have demonstrated that immune checkpoint co-inhibitory receptor-blocking antibodies can revert tumor-induced immunosuppression and augment overall anti-tumor immunity. These antibodies induced durable clinical responses and unprecedented therapeutic benefits in multiple types of malignancies. Although immune checkpoint inhibitors have revolutionized cancer therapy, the clinical benefits of these drugs have been limited to subsets of cancer patients and treatments frequently associated with a unique spectrum of toxicities, termed immune-related adverse events. Future discoveries of novel immune checkpoint receptors, identification of new prognostic and predictive biomarkers, and improvement of combination therapies are likely to boost the success rate of cancer immunotherapy and increase the survival rates of patients with different types of cancers.

Keywords: Immune checkpoint, Immunotherapy, Cancer, Autoimmune diseases, T lymphocytes

Core tip: The major functions of immune checkpoint receptors are to maintain self-tolerance, prevent immunopathology, and regulate overall immune homeostasis. However, skewed activation of these receptors by cancer cells may lead to suppression of nascent anti-tumor immunity and promote tumor cell growth. Clinical studies have demonstrated that blocking inhibitory immune checkpoint receptors induced durable clinical responses and unprecedented therapeutic benefits in multiple types of malignancies. The present editorial addresses some of the major immune checkpoint receptor targets in cancer immunotherapy, discusses some of the side effects and limitations in their utilization, and highlights some of the future challenges in the field.