Huang WT, Zhang BB, Zhao JN. Letter to the Editor: Autoantibody profiling in gastric cancer immunotherapy - dynamic monitoring, toxicity-benefit trade-off, and immune endotypes. World J Gastroenterol 2026; 32(36): 120350 [DOI: 10.3748/wjg.120350]
Corresponding Author of This Article
Jia-Nan Zhao, Academic Fellow, Department of Cardiovascular Sciences, Temple University, North Carlisle Street, 3440 Carlisle st, Philadelphia, PA 19140, United States. tuv36393@temple.edu
Research Domain of This Article
Immunology
Article-Type of This Article
letter
Open-Access Policy of This Article
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/
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
Share the Article
Huang WT, Zhang BB, Zhao JN. Letter to the Editor: Autoantibody profiling in gastric cancer immunotherapy - dynamic monitoring, toxicity-benefit trade-off, and immune endotypes. World J Gastroenterol 2026; 32(36): 120350 [DOI: 10.3748/wjg.120350]
World J Gastroenterol. Sep 28, 2026; 32(36): 120350 Published online Sep 28, 2026. doi: 10.3748/wjg.120350
Letter to the Editor: Autoantibody profiling in gastric cancer immunotherapy - dynamic monitoring, toxicity-benefit trade-off, and immune endotypes
Wan-Ting Huang, Bin-Bin Zhang, Jia-Nan Zhao
Wan-Ting Huang, School of Public Health and Nursing, Hangzhou Normal University, Hangzhou 311121, Zhejiang Province, China
Bin-Bin Zhang, School of Clinical Medicine, Hangzhou Normal University, Hangzhou 311121, Zhejiang Province, China
Jia-Nan Zhao, Department of Cardiovascular Sciences, Temple University, Philadelphia, PA 19140, United States
Co-corresponding authors: Bin-Bin Zhang and Jia-Nan Zhao.
Author contributions: Huang WT performed the literature retrieval and evidence synthesis, organized the references, and drafted the original manuscript; Zhang BB and Zhao JN conceptualized and designed the study framework, defined the academic positioning and core perspectives, provided substantial intellectual input, critically revised the manuscript for key scientific content, and supervised the entire work; they contributed equally to this article, they are the co-corresponding authors of this manuscript; and all authors reviewed and approved the final submitted version.
Supported by National Natural Science Foundation of China, No. 82204827.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Jia-Nan Zhao, Academic Fellow, Department of Cardiovascular Sciences, Temple University, North Carlisle Street, 3440 Carlisle st, Philadelphia, PA 19140, United States. tuv36393@temple.edu
Received: February 24, 2026 Revised: April 4, 2026 Accepted: May 12, 2026 Published online: September 28, 2026 Processing time: 178 Days and 14.9 Hours
Abstract
A study by Zheng et al published in the World Journal of Gastroenterology has reported that antinuclear antibody (ANA) and extractable nuclear antigen (ENA) positivity, together with carcinoembryonic antigen and tumor-node-metastasis stage, independently predict outcomes in gastric cancer patients receiving anti-programmed death 1/programmed death-ligand 1 based immunotherapy. However, although the findings of these authors support the clinical relevance of host autoimmunity, we believe that the implications can be further extended in three directions. Firstly, dependence on a single baseline ANA/ENA measurement overlooks the longitudinal dynamics that may distinguish pre-existing autoimmunity from treatment-induced seroconversion, which could be differentially associated with a durable response and acquired resistance. Secondly, interpreting ANA/ENA purely as a favorable prognostic marker neglects their potential value in signaling a heightened risk of immune-related adverse events, thereby indicating a need to evaluate the net clinical benefit rather than survival alone. Thirdly, the binary definition of ANA/ENA positivity ignores immunofluorescence patterns and specific ENA components that might define distinct “autoantibody immune endotypes” with different tumor-immune microenvironments. To refine immunotherapy-oriented risk stratification in gastric cancer, we propose prospective studies that integrate dynamic autoantibody profiling, detailed patterns, and toxicity data within composite host-tumor models.
Core Tip: Baseline antinuclear antibody/extractable nuclear antigen status may serve as a potential predictor of immunotherapy outcomes in gastric cancer. However, static indicators fail to capture dynamic autoantibody changes or the underlying differences in immune endotypes. We propose to build a composite host-tumor model that integrates longitudinal antibody profiles, detailed staining patterns, and safety data, and apply calibration curves and decision curve analysis to evaluate its net clinical benefit, thereby promoting the establishment of more refined risk stratification strategies and facilitating the practice of personalized immuno-oncology.
