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World J Gastrointest Oncol. Jan 15, 2022; 14(1): 19-37
Published online Jan 15, 2022. doi: 10.4251/wjgo.v14.i1.19
Biomarkers for response to immune checkpoint inhibitors in gastrointestinal cancers
Meng Li, Denis Kaili, Lei Shi
Meng Li, Lei Shi, School of Life Sciences, Chongqing University, Chongqing 400044, China
Denis Kaili, Department of Surgery, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, United States
Author contributions: Li M and Shi L participated in the design of the study, and prepared the tables and figure; Li M, Kaili D, and Shi L participated in writing the manuscript; all authors have read and approved the final manuscript.
Supported by Fundamental Research Funds for the Central Universities, No. 2019CDYGYB024.
Conflict-of-interest statement: The authors declare no competing or financial interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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:
Corresponding author: Lei Shi, PhD, Associate Professor, School of Life Sciences, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China.
Received: February 22, 2021
Peer-review started: February 22, 2021
First decision: August 19, 2021
Revised: September 8, 2021
Accepted: December 21, 2021
Article in press: December 21, 2021
Published online: January 15, 2022

Gastrointestinal (GI) cancers account for a large proportion of cancer deaths worldwide and pose a major public health challenge. Immunotherapy is considered to be one of the prominent and successful approaches in cancer treatment in recent years. Among them, immune checkpoint inhibitor (ICI) therapy, has received widespread attention, and many clinical findings support the feasibility of ICIs, with sustained responses and significantly prolonged lifespan observed in a wide range of tumors. However, patients treated with ICIs have not fully benefited, and therefore, the identification and development of biomarkers for predicting ICI treatment response have received further attention and exploration. From tumor genome to molecular interactions in the tumor microenvironment, and further expanding to circulating biomarkers and patient characteristics, the exploration of biomarkers is evolving with high-throughput sequencing as well as bioinformatics. More large-scale prospective and specific studies are needed to explore biomarkers in GI cancers. In this review, we summarize the known biomarkers used in ICI therapy for GI tumors. In addition, some ICI biomarkers applied to other tumors are included to provide insights and further validation for GI tumors. Moreover, we present single-cell analysis and machine learning approaches that have emerged in recent years. Although there are no clear applications yet, it can be expected that these techniques will play an important role in the application of biomarker prediction.

Keywords: Immunotherapy, Immune checkpoint inhibitor, Biomarker, Predictive response, Gastrointestinal cancer

Core Tip: Cancer immunotherapy and immune checkpoint inhibitors (ICIs) have recently revolutionized gastrointestinal (GI) cancer treatment, providing unprecedented clinical benefits. However, GI patients treated with ICIs do not fully benefit, and therefore, the identification and development of biomarkers for predicting ICI response have become a pressing issue to be solved now. In this review, we summarize the use of predictive biomarkers for ICI treatment response in GI cancers, and discuss novel biomarkers under development. We also present important biomarkers in other tumors with the aim of providing a cutting-edge reference for GI cancer research.