A serpin-myeloid axis in pancreatic cancer heterogeneity and immune evasion.

Serpine1 and Serpinb2 drive immune evasion in pancreatic ductal carcinoma by shaping immunosuppressive microenvironments in spatially restricted niches.

• Why it matters: Understanding how tumor heterogeneity influences immune resistance is crucial for improving immunotherapy strategies in pancreatic cancer, which is notoriously resistant.
• What they did: Using spatial functional genomics, the study identified SERPINE1 and SERPINB2 as key regulators that promote fibrin-rich niches, retain immunosuppressive macrophages, and exclude cytotoxic T cells across tumor regions.
• The result: Targeting PAI1, PAI2, or their pathways enhances tumor control and synergizes with anti-PD-1 therapy, revealing potential avenues to overcome immune evasion driven by tumor-intrinsic heterogeneity.