The abscopal effect of radioimmunotherapy, wherein tumor shrinkage occurs beyond the irradiated field, is therapeutically promising but clinically rare. The mechanisms underlying this effect remain elusive. Here, in vivo genome-wide CRISPR screening identifies SFRP2 as a potential stromal regulator of the abscopal effect. SFRP2 exhibits cancer-associated fibroblast (CAF)-specific expression and radioimmunotherapy-mediated upregulation in unirradiated tumors. Conditional Sfrp2 knockout in CAFs boosts the abscopal effect by rewiring the vascular-immune microenvironment to promote CD8