A serpin–myeloid axis in pancreatic cancer heterogeneity and immune evasion

SERPINE1 and SERPINB2 drive the formation of fibrin-rich niches in pancreatic ductal adenocarcinoma that locally reprogram macrophages toward an immunosuppressive phenotype and exclude cytotoxic T cells, establishing spatially organized immune evasion. The study, published in Nature, reveals a mechanistic serpin–myeloid axis that explains intra-tumoral heterogeneity in immune infiltration across distinct microenvironmental compartments. These findings identify serpins and their downstream fibrin signaling as potential therapeutic targets to overcome the notoriously immunosuppressive stroma of pancreatic cancer.