Review
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2024; 30(16): 2195-2208
Published online Apr 28, 2024. doi: 10.3748/wjg.v30.i16.2195
Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer
Xiao-Jun Zhang, Yan Yu, He-Ping Zhao, Lei Guo, Kun Dai, Jing Lv
Xiao-Jun Zhang, Yan Yu, He-Ping Zhao, Jing Lv, Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
Lei Guo, Department of Spinal Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
Kun Dai, Department of Clinical Laboratory, Yanliang Railway Hospital of Xi’an, Xi’an 710089, Shaanxi Province, China
Co-first authors: Xiao-Jun Zhang and Yan Yu.
Author contributions: Zhang XJ and Lv J searched and reviewed published articles, wrote and revised the manuscript, and made substantial contributions to the conception and design of this study; Zhang XJ, Yu Y, Zhao HP, Guo L, Dai K, and Lv J critically reviewed and revised the manuscript; and all authors have read and approved the final manuscript.
Supported by Xi’an Municipal Health Commission of China, No. 2022qn07 and No. 2023ms11.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jing Lv, MD, Doctor, Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, No. 555 Youyi Dong Road, Xi’an 710054, Shaanxi Province, China. lvjing-1219@163.com
Received: January 26, 2024
Revised: March 5, 2024
Accepted: April 10, 2024
Published online: April 28, 2024
Processing time: 91 Days and 7.1 Hours
Abstract

As a highly invasive malignancy, esophageal cancer (EC) is a global health issue, and was the eighth most prevalent cancer and the sixth leading cause of cancer-related death worldwide in 2020. Due to its highly immunogenic nature, emer-ging immunotherapy approaches, such as immune checkpoint blockade, have demonstrated promising efficacy in treating EC; however, certain limitations and challenges still exist. In addition, tumors may exhibit primary or acquired resistance to immunotherapy in the tumor immune microenvironment (TIME); thus, understanding the TIME is urgent and crucial, especially given the im-portance of an immunosuppressive microenvironment in tumor progression. The aim of this review was to better elucidate the mechanisms of the suppressive TIME, including cell infiltration, immune cell subsets, cytokines and signaling pathways in the tumor microenvironment of EC patients, as well as the downregulated expression of major histocompatibility complex molecules in tumor cells, to obtain a better understanding of the differences in EC patient responses to immunotherapeutic strategies and accurately predict the efficacy of immunotherapies. Therefore, personalized treatments could be developed to maximize the advantages of immunotherapy.

Keywords: Esophageal cancer; Esophageal squamous cell carcinoma; Esophageal adenocarcinoma; Tumor immune microenvironment; Immunosuppression; Immu-notherapy

Core Tip: Esophageal cancer (EC) is a significant global health issue, and immunotherapy holds promise for treating this disease. However, resistance to immunotherapy may occur, and is usually associated with the tumor immune microenvironment (TIME). Understanding the TIME, especially the suppressive TIME, is crucial. The aim of this review is to elucidate the underlying mechanisms of the suppressive TIME in EC, including cell infiltration, immune cell subsets, cytokines and signaling pathways, as well as the downregulated expression of major histocompatibility complex molecules in tumor cells. This summary may help predict EC patient responses to immunotherapies and facilitate personalized treatments to optimize immunotherapeutic outcomes.