Spatial immune niches provide a framework for understanding immunotherapy resistance in gastric cancerSpatial Immune Niches May Help Explain Gastric Cancer Treatment Response

This narrative review synthesizes findings from clinical trials, single-cell/spatial multi-omics, multiplex IHC/IF, and digital pathology to explore the role of spatial immune niches in gastric cancer and gastroesophageal junction adenocarcinoma. The authors define these niches as tissue compartments shaped by malignant-cell states, effector-cell access, tertiary lymphoid structures, cancer-associated fibroblasts, tumor-associated macrophages, extracellular matrix, vascular function, and metastatic-site ecology.

The primary finding is that these spatial immune niches shape the patient response to immunotherapy. Specifically, the review identifies several niche types, including lymphoid-organized inflamed, inflamed-but-suppressed, stromal-excluded, myeloid-dominant, vascular/hypoxic, target-antigen-associated, and peritoneal metastatic. These compartments are proposed as a framework for interpreting mechanisms of immune resistance.

A noted limitation is that the review synthesizes diverse data types rather than providing specific clinical trial results or statistical evidence for individual niche types. Clinical application remains preliminary; however, the authors suggest that compact spatial assays may eventually refine patient selection and support niche-matched combination strategies. The findings are currently framed as a conceptual model for understanding resistance rather than established causal links.