RT reshapes the TME through multiple mechanisms. (A) Moderate or fractionated RT leads to vascular normalization by upregulating endothelial adhesion molecules (ICAM-1, VCAM-1, and E-selectin) and chemokine production (CXCL9, CXCL10, and CXCL11) to promote lymphocyte infiltration, thereby enhancing antitumor immunity and facilitating the transition from cold to hot tumors. In contrast, following high ablative doses, radiation-driven cytokines (CCL2, CCL5, TGF-β, etc.) recruit and expand Tregs, MDSCs, M2-polarized macrophages, regulatory B cells (Bregs), and γδ T cells, which dampen CD8⁺ T cell responses via IL-10, arginase-1, and TGF-β. These doses induce vascular damage and hypoxia, activating HIF-1α/SDF-1 signaling to recruit immunosuppressive myeloid populations. (B) mregDCs serve as a pivotal hub. By forming cellular triads with CXCL13⁺ helper T cells and T_PEX cells, mregDCs promote effector differentiation through IL-15 transpresentation and CXCL16 secretion. In contrast, mregDCs also recruit Tregs via CCL22/CCL17 and engage activated Tregs through antigen presentation and coregulatory receptor–ligand interactions, including MHC II–TCR, OX40L–OX40, PD-L1–PD-1, and CD80/86–CTLA-4, thereby supporting Treg activation and reinforcing local immunosuppression.