To interpret immunotherapy resistance in gastric and gastroesophageal junction adenocarcinoma through a spatial immune-ecology lens.
Approach:
Spatial Immune Ecology Framework: The review organizes gastric and gastroesophageal junction adenocarcinoma into immune ecosystems based on immune accessibility, competence, and suppression.
Key Findings:
Current biomarkers, including PD-L1 scoring and microsatellite instability, do not fully explain the ability of antitumor immunity to engage with malignant tissue.
Spatial features such as tumor-nest CD8+ infiltration and tertiary lymphoid structure maturity complement established biomarkers.
Immune checkpoint inhibitors exhibit variable clinical responses due to primary, adaptive, and acquired resistance mechanisms influenced by tumor-intrinsic programs and microenvironmental constraints.
Interpretation:
Immunotherapy resistance is interpreted as a lesion-level issue influenced by the spatial organization of immune and tumor cells, rather than solely by molecular biomarkers.
Limitations:
The spatial evidence base is uneven across gastric and gastroesophageal junction adenocarcinoma, with most studies focusing on gastric cancer cohorts.
Findings from gastric cancer cohorts may not automatically apply to gastroesophageal junction adenocarcinoma.
Conclusion:
Spatial immune ecology provides a framework for understanding immunotherapy resistance, highlighting the need for further prospective testing of spatial features in treatment-linked cohorts.
