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

Highlights

– A distinct PDE5A+ CAF subpopulation is associated with shorter overall survival and an immune‑excluded tumour microenvironment (TME) in gastric cancer (GC).

– PDE5A+ CAFs promote ECM remodelling and epithelial–mesenchymal transition (EMT) and activate PI3K/AKT/mTOR signalling to secrete CXCL12, recruiting CXCR4+ LAG3+ exhausted CD8 T cells.

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