Review
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Aug 15, 2025; 17(8): 109489
Published online Aug 15, 2025. doi: 10.4251/wjgo.v17.i8.109489
Unmasking immune checkpoint resistance in esophageal squamous cell carcinoma: Insights into the tumor microenvironment and biomarker landscape
Zhe Wang, Rui-Ying Zhang, Yi-Fan Xu, Bing-Tong Yue, Jia-Yi Zhang, Feng Wang
Zhe Wang, Rui-Ying Zhang, Feng Wang, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Yi-Fan Xu, Bing-Tong Yue, Jia-Yi Zhang, Department of Clinical Medicine, The First Clinical Medical College of Zhengzhou University, Zhengzhou 45000, Henan Province, China
Co-first authors: Zhe Wang and Rui-Ying Zhang.
Co-corresponding authors: Jia-Yi Zhang and Feng Wang.
Author contributions: Wang Z and Zhang RY contributed equally to this work as co-first authors; Zhang JY and Wang F contributed equally to this work as co-corresponding authors; Wang Z drafted the original manuscript; Zhang RY, Xu YF and Yue BT carried out the literature search and helped structure the review; Zhang JY and Wang F conceived and supervised the study and made critical revisions; all authors prepared the draft and approved the submitted version.
Conflict-of-interest statement: The authors declare no conflict of 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Feng Wang, MD, PhD, Professor, Senior Researcher, Senior Scientist, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No. 50 Eastern Jianshe Road, Zhengzhou 450052, Henan Province, China. zzuwangfeng@zzu.edu.cn
Received: May 13, 2025
Revised: June 2, 2025
Accepted: July 16, 2025
Published online: August 15, 2025
Processing time: 93 Days and 15 Hours
Core Tip

Core Tip: Esophageal squamous cell carcinoma (ESCC) poses significant clinical challenges due to its aggressive progression and poor survival outcomes. While immunotherapy offers promise, resistance—both primary and acquired—remains a major hurdle, limiting its efficacy. This review explores the mechanisms of immunotherapy resistance in ESCC, including immunosuppressive cells, inhibitory cytokines, and molecular alterations in programmed death 1/programmed death-ligand 1 signaling. We also examine emerging strategies to overcome resistance, such as combination therapies and tumor microenvironment remodeling, emphasizing the need for predictive biomarkers to improve patient outcomes.