(A) pDCs enter the tumor environment, in which they can capture and present tumor antigens through class I (MHC I) and class II (MHC II) major histocompatibility molecules to CD8⁺ and CD4⁺ T cells specific for the antigen. Environmental signals drive the expression of Foxo3 that in turn controls the de novo synthesis of the amino acid–metabolizing enzymes IDO and ARG1, the cytokine TGF-β, and the surface inhibitory molecule PD-L1. After interaction with CD8⁺ T cells, Foxo3-expressing pDCs enforce conversion of CD8⁺ T cells into Tregs, which then block proliferation and effector functions on nearby CD8⁺ T lymphocytes, recognizing either the same or other tumor antigens. (B) This immunosuppressive network is disrupted by the generation of tumor-antigen specific CD4⁺ T cells that engage pDCs, turn off Foxo3, and make pDCs capable of fully stimulating CD8⁺ T cells, allowing their proliferation and acquisition of effector function, as highlighted by the recovered ability to release IFN-γ and recognize cancer cells.