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

This raises the question of whether immune resistance is a global tumor property or organized within spatially restricted niches. Using Perturb-map spatial functional genomics, we determine how different genes shape the growth and cellular environments of PDAC clones across space and time.

This revealed early gene-driven remodeling of local immune neighborhoods preceding late-stage spatial clonal dominance. We identify SERPINE1 (PAI1) and SERPINB2 (PAI2) as dominant regulators of tumor microenvironment control and immune evasion. These SERPINs promote stabilization of fibrin-rich ECM niches that spatially retain and program macrophages toward immunosuppressive states while excluding cytotoxic T cells.