Check out the preprint for all the data, figures, and amazing co-authors!
@brownlab1.bsky.social #ImmunoOncology #CRISPRscreen #SpatialBiology #ECM #PDAC #CancerImmunology
(8/8)

This changes our view of the ECM: It’s not just a passive barrier, but an active player in immune evasion.
(7/8)

Deleting Serpine1 or Serpinb2:
✓ Remodels the ECM
✓ Reduces immunosuppressive macrophage accumulation
✓ Permits T cell infiltration
✓ Synergizes with anti-PD-1 immunotherapy, increasing survival
(6/8)

⭐️ Key finding: Loss of Serpine1 (PAI-1) or Serpinb2 (PAI-2) impairs tumor fitness in an immune-dependent way. These serpins shape a fibrin-rich ECM that recruits macrophages, building local immunosuppressive niches. (5/8)

We applied Perturb-map (Dhainaut et al., Cell 2022) to perform a spatial CRISPR screen of extracellular factors in orthotopic PDAC models.
This let us track over space and time:
✓ Clonal selection
✓ TME remodeling
✓ Immune reprogramming
(4/8)

Why?
The PDAC tumor microenvironment (TME) is dense, fibrotic, and profoundly immunosuppressive. T cells are excluded or suppressed, and the extracellular matrix (ECM) may physically and functionally block immune infiltration.
But how ECM components do this is still unclear. (3/8)

#PDAC is one of the deadliest cancers—and is on track to become the 2nd leading cause of cancer death. (2/8)