Evolving landscape of the gastric cancer immune microenvironment: From spatial architecture to precision biomarkers

Table 1 Comparative spatial and molecular metrics of gastric cancer tumor immune microenvironment phenotypes

Metric	Immune-inflamed (“hot“)	Immune-excluded (“cold“)	Immune-desert (“cold“)
Predominant subtype	Epstein-Barr virus+, microsatellite instability-high	Genomically stable (genomically stable)	Chromosomal Instability
Dominant chemokine axis	CXCL9/10/11-CXCR3	CXCL12-CXCR4	Low/absent
B-cell/TLS organization	Mature TLS (secondary follicles) with gastric cancer reaction; high B-cell diversity	Immature TLS or disorganized B-cell aggregates at the margin	Absent or rare B-cell clusters; lack of TLS formation
Stroma density (collagen)	Low/moderate	High (cross-linked lysyl oxidase-like 2 + fibers)	Variable
T-cell factor 1 + T-cell niche	Present in mature TLS	Restricted to invasive margin 15	Absent
Response to anti-programmed cell death protein 1	High (50%-70%)	Low (primary resistance)	Negligible

CXCL: C-X-C motif chemokine ligand; CXCR: C-X-C motif chemokine receptor; TLS: Tertiary lymphoid structure.