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Androgen signaling as evidenced in castration therapy studies, manipulates this immunosuppressive network by inhibiting arginine metabolism via two synergistic pathways: 1) Myeloid-derived suppressor cells (e.g., CD11b + cells) overexpressing ARG1 deplete extracellular L-arginine, crippling T-cell function through CD3 chain downregulation, impaired antigen recognition, and dual activation of the GCN2-eIF2 stress pathway with concurrent mTOR suppression (185187)