[Comprehensive Analysis of Spatial and Temporal Tumor Heterogeneity of Immune Checkpoint Molecules in GastricCancer]

The introduction of immune checkpoint inhibitors (ICIs) has led to significant advances in the treatment of gastric cancer. Immune-related biomarkers, including PD-L1 expression, are currently used to guide therapeutic decision‒making; however, recent studies have highlighted the complex biological heterogeneity underlying tumor-immune interactions in gastric cancer. Tumors exhibit spatial heterogeneity, with region-specific molecular and immune profiles, as well as temporal heterogeneity, characterized by dynamic changes in immune features in response to treatment and over time. Advances in single-cell analyses and spatial transcriptomics have further demonstrated that immunosuppressive tumor ecosystems can be spatially localized, and that therapeutic interventions themselves may influence the expression dynamics of immune checkpoint molecules. In this review, we focus on immune checkpoint molecules in gastric cancer and summarize current insights into spatial and temporal tumor heterogeneity, discussing their clinical implications and considerations for the interpretation of immunerelated biomarkers.