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Yunus Emre Demirhan
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MINI-REVIEW

Immunotherapy in esophageal, gastric/gastroesophageal junction, and colorectal cancers: Biomarker selection, current practice, and future directions

Yunus Emre Demirhan1* ,  Mohamed Lotfi Messouak2 ,  Arshdeep Gill2 ,  Adam Soltani2 ,  Samir Dalia3
CP, 026210034 https://doi.org/10.36922/CP026210034
Received: 19 May 2026 | Revised: 9 June 2026 | Accepted: 1 July 2026 | Published online: 14 July 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

The management of advanced gastrointestinal malignancies now relies heavily on biomarker-driven immunotherapy. In esophageal, gastric/gastroesophageal junction (GEJ), and colorectal cancers, the clinical utility of immune checkpoint blockade is governed by tumor histology, mismatch repair status, and programmed death-ligand 1 (PD-L1) expression. Microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) status remains the most consistent predictor of durable immunotherapy benefit, enabling treatment de-escalation strategies in selected MSI-H/dMMR settings. Conversely, upper gastrointestinal adenocarcinomas require integration of overlapping biomarkers, including PD-L1 combined positive score, human epidermal growth factor receptor 2, and claudin 18.2, to guide immunotherapy-based and targeted treatment strategies. Major therapeutic gaps remain in microsatellite-stable colorectal cancer, where spatial heterogeneity, liver-mediated immune tolerance, and an immune-excluded microenvironment render tumors largely refractory to standard checkpoint inhibition. Accordingly, this narrative review focuses on practical biomarker selection, resistance mechanisms, and evidence-level distinctions across selected gastrointestinal cancers.

Keywords
Immunotherapy
Esophageal cancer
Gastric cancer
Gastroesophageal junction cancer
Colorectal cancer
Biomarkers
Immune checkpoint inhibitors
Microsatellite instability
Funding
None.
Conflict of interest
The authors declare no conflicts of interest related to this work.
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