Review
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Apr 15, 2019; 11(4): 270-280
Published online Apr 15, 2019. doi: 10.4251/wjgo.v11.i4.270
Identification of genomic features associated with immunotherapy response in gastrointestinal cancers
Yin He, Zhi-Xian Liu, Ze-Hang Jiang, Xiao-Sheng Wang
Yin He, Zhi-Xian Liu, Ze-Hang Jiang, Xiao-Sheng Wang, Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, Nanjing 211198, Jiangsu Province, China
Yin He, Zhi-Xian Liu, Ze-Hang Jiang, Xiao-Sheng Wang, Cancer Genomics Research Center, School of Basic Medicine and Clinical Pharmacy, Nanjing 211198, Jiangsu Province, China
Yin He, Zhi-Xian Liu, Ze-Hang Jiang, Xiao-Sheng Wang, Big Data Research Institute, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China
Author contributions: He Y performed the study and wrote the manuscript. Liu ZX wrote the manuscript; Jiang ZH performed data analyses; Wang XS conceived of and designed the study and wrote the manuscript.
Supported by the China Pharmaceutical University, No: 3150120001.
Conflict-of-interest statement: No potential conflicts 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: Xiao-Sheng Wang, MD, PhD, Associate Professor, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China. xiaosheng.wang@cpu.edu.cn
Telephone: +86-186-0129-9809
Received: January 2, 2019
Peer-review started: January 4, 2019
First decision: January 21, 2019
Revised: January 29, 2019
Accepted: March 27, 2019
Article in press: March 28, 2019
Published online: April 15, 2019
Processing time: 103 Days and 8.4 Hours
Abstract

Gastrointestinal (GI) cancers prevail and account for an extremely high number of cancer deaths worldwide. The traditional treatment strategies, including surgery, chemotherapy, radiotherapy, and targeted therapy, have a limited therapeutic effect for advanced GI cancers. Recently, immunotherapy has shown promise in treating various refractory malignancies, including the GI cancers with mismatch repair deficiency (dMMR) or microsatellite instability (MSI). Thus, immunotherapy could be a promising treatment approach for GI cancers. Unfortunately, only a small proportion of GI cancer patients currently respond to immunotherapy. Therefore, it is important to discover predictive biomarkers for stratifying GI cancer patients response to immunotherapy. Certain genomic features, such as dMMR/MSI, tumor mutation burden (TMB), and tumor aneuploidy have been associated with tumor immunity and im-munotherapy response and may serve as predictive biomarkers for cancer immunotherapy. In this review, we examined the correlations between tumor immunity and three genomic features: dMMR/MSI, TMB, and tumor aneuploidy. We also explored their correlations using The Cancer Genome Atlas data and confirmed that the dMMR/MSI status, high TMB, and low tumor aneuploidy are associated with elevated tumor immunity in GI cancers. To improve the immunotherapeutic potential in GI cancers, more genetic or genomic features associated with tumor immune response need to be identified. Furthermore, it is worth exploring the combination of different immunotherapeutic methods and the combination of immunotherapy with other therapeutic approaches for cancer therapy.

Keywords: Gastrointestinal cancer; Tumor immunity; Tumor immunotherapy; DNA mismatch repair; Tumor mutation burden; Tumor aneuploidy

Core tip: The traditional treatment strategies have a limited effect on advanced gastrointestinal (GI) cancers. Immunotherapy has shown improved effectiveness in treating diverse malignancies, including the GI cancers with mismatch repair deficiency (dMMR) or microsatellite instability (MSI). However, only a small subset of GI cancers can benefit from immunotherapy. Hence, it is crucial to identify predictive biomarkers for GI cancer patients responsive to immunotherapy. We reviewed the associations between three genomic features (dMMR/MSI, tumor mutation burden, and aneuploidy) and tumor immunity. These genomic features have significant correlations with antitumor immune response and are useful biomarkers for immunotherapy of GI cancers.