In pancreatic ductal adenocarcinoma (PDAC), agonistic anti-CD40 (αCD40) activates dendritic cells (DCs) to drive antitumor immunity, yet the mechanistic workings of αCD40 intratumorally were only partially understood. Here, we leveraged spatiotemporal imaging and lineage tracing approaches to define how CD40-activated DCs reshape intratumoral regulatory T cell (Treg) cell fate in a mouse model of PDAC, where immune checkpoint blockade (αPD-1 + αCTLA-4) combined with αCD40 controls tumor growth. Following treatment, intratumoral Foxp3⁺ Treg cells rapidly declined in a manner dependent on DC-derived interleukin (IL)-12 and downstream interferon (IFN)-γ signaling. Rather than simple depletion, this reflected a DC-driven reprogramming event in which Treg cells acquired an “ExTreg” phenotype marked by loss of Foxp3 and acquisition of T helper 1 (Th1)-like features (T-bet⁺ IFN-γ⁺). αCD40 induced a spatially reorganized tumor microenvironment, establishing a DC-rich niche at the tumor border where CXCL9-expressing DCs colocalized with CXCR3⁺ Treg and ExTreg cells. In situ analysis of T cell receptor signaling revealed that ExTreg cells exhibited the highest levels of antigen-driven activation among tumor-infiltrating T cells, and aligned closely with local DC-mediated priming. Together, these findings identify CD40-activated DCs as spatial and functional orchestrators of Treg plasticity, converting suppressive cells into Th1-like effectors with antitumor potential.