Takahashi K. Stage-dependent prognostic value of programmed death ligand-1 expression in gastric cancer: Implications for personalized immunotherapy. World J Gastroenterol 2026; 32(34): 118762 [DOI: 10.3748/wjg.118762]
Corresponding Author of This Article
Koji Takahashi, MD, Department of Gastroenterology, Eastern Chiba Medical Center, 3-6-2, Okayamadai, Togane 283-8686, Chiba, Japan. koji517@gmail.com
Research Domain of This Article
Gastroenterology & Hepatology
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review-article
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Takahashi K. Stage-dependent prognostic value of programmed death ligand-1 expression in gastric cancer: Implications for personalized immunotherapy. World J Gastroenterol 2026; 32(34): 118762 [DOI: 10.3748/wjg.118762]
World J Gastroenterol. Sep 14, 2026; 32(34): 118762 Published online Sep 14, 2026. doi: 10.3748/wjg.118762
Stage-dependent prognostic value of programmed death ligand-1 expression in gastric cancer: Implications for personalized immunotherapy
Koji Takahashi
Koji Takahashi, Department of Gastroenterology, Eastern Chiba Medical Center, Togane 283-8686, Chiba, Japan
Koji Takahashi, Department of General Medical Science, Graduate School of Medicine, Chiba University, Chiba 260-8677, Japan
Author contributions: Takahashi K wrote the original draft.
Conflict-of-interest statement: The author reports no relevant conflicts of interest for this article.
Corresponding author: Koji Takahashi, MD, Department of Gastroenterology, Eastern Chiba Medical Center, 3-6-2, Okayamadai, Togane 283-8686, Chiba, Japan. koji517@gmail.com
Received: January 12, 2026 Revised: January 31, 2026 Accepted: March 10, 2026 Published online: September 14, 2026 Processing time: 221 Days and 11.7 Hours
Abstract
The integration of immune checkpoint inhibitors has fundamentally altered treatment strategies for advanced gastric and gastroesophageal junction cancer. However, the prognostic and predictive utility of programmed death ligand-1 (PD-L1) expression remains a subject of intense debate due to its inherent biological complexity. While large-scale meta-analyses generally suggest that high PD-L1 expression correlates with poorer overall survival, clinical outcomes in trials of PD-1 blockade show significant heterogeneity. This review reappraises PD-L1 not as a static marker, but as a dynamic reflection of the tumor microenvironment. We discuss the biological framework of the three major immune phenotypes - immune-inflamed, immune-excluded, and immune-desert - as the basis for understanding clinical response. Furthermore, we examine the influence of molecular subtypes, such as Epstein-Barr virus and microsatellite instability, and evaluate evidence from pivotal phase III trials in both metastatic and perioperative settings. By moving beyond simplified scoring systems and acknowledging the stage-dependent and subtype-specific biological realities, we propose a more personalized approach to immunotherapy in gastric cancer.
Core Tip: This review reappraises programmed death ligand-1 expression in gastric cancer and gastroesophageal junction cancer as a dynamic reflection of the tumor microenvironment. We examine the stage-dependent prognostic shift of programmed death ligand-1 and immune phenotypes (inflamed, excluded, and desert). By integrating phase III trial data with molecular subtypes like Epstein-Barr virus and microsatellite instability, we highlight limitations of simplified scoring. We propose personalized immunotherapy, driven by spatial analysis and dynamic monitoring, to optimize outcomes across the complex biological landscape of gastric cancer.
