Claudin18.2 positive gastric cancer: biology, tumor microenvironment, and therapeutic strategies.

Claudin18.2 (CLDN18.2) is primarily expressed in gastric epithelial cells, where it plays a crucial role in maintaining the integrity of the gastric mucosal barrier. Its aberrant expression is closely associated with the initiation, progression, and tumor microenvironment (TME) remodeling of gastric cancer(GC). Clinical evidence indicates that CLDN18.2 is highly expressed in a substantial proportion of GC. Notably, its expression appears to be largely independent of established biomarkers such as human epidermal growth factor receptor 2 (HER2) and programmed death-ligand 1 (PD-L1). These features collectively suggest CLDN18.2 as a viable candidate for therapeutic intervention in GC. Increasing evidence suggests that CLDN18.2 positivity is associated with patient prognosis and may indicate a distinctive TME characterized by increased infiltration of CD4⁺ and CD8⁺ T cells, macrophages, and cancer-associated fibroblasts. This review systematically summarizes the biological characteristics of CLDN18.2 and the features of CLDN18.2-positive TME, and provides an overview of emerging therapeutic strategies targeting CLDN18.2. The aim is to elucidate the biological and clinical significance of CLDN18.2 in GC and to provide insights for optimizing future precision therapies.