PDE5A-Positive Cancer-Associated Fibroblasts Drive Immune Exclusion in Gastric Cancer — Therapeutic Rationale for Combining PDE5 Inhibition with LAG3 Blockade

PDE5A-Positive Cancer-Associated Fibroblasts Drive Immune Exclusion in Gastric Cancer — Therapeutic Rationale for Combining PDE5 Inhibition with LAG3 Blockade

Single‑cell and spatial profiling identify a PDE5A+ CAF subset that remodels stroma, activates PI3K/AKT/mTOR–CXCL12 signaling, and recruits exhausted LAG3+ CD8 T cells, promoting immune exclusion in gastric cancer. Vardenafil plus LAG3 blockade restores antitumour immunity in preclinical models, supporting biomarker‑driven combination trials.