Dendritic cell-driven immune rebalancing as a systemic regulator of tumor and neurodegenerative microenvironments

Dendritic cells (DCs) critically regulate immune dynamics within the tumor microenvironment (TME), yet the mechanisms governing the balance between effective anti-tumor immunity and immune tolerance remain incompletely defined. Existing reviews have largely examined DC biology, tumor immunology and neuroinflammation within disease-specific frameworks, leaving insufficient attention to how DC dysfunction may be compared across chronic pathological microenvironments. Here, we propose DC-driven immune rebalancing as a context-dependent framework for understanding how antigen-presenting cell states, inflammatory signaling, metabolic conditioning and immune-resolution circuits shape divergent disease outcomes. Within the TME, hypoxia, lactate accumulation, aberrant cytokine signaling and stromal-vascular constraints can reprogram DCs toward dysfunctional or tolerogenic states, thereby impairing antigen presentation, weakening T-cell priming and limiting durable anti-tumor responses. In neurodegenerative disease, immune imbalance is more commonly characterized by persistent peripheral-central inflammatory activation, regulatory insufficiency and defective resolution, rather than by tumor-like immune tolerance. We therefore do not argue that cancer and neurodegeneration share identical DC phenotypes. Instead, we suggest that both disease contexts can be compared through disrupted DC-centered immune-regulatory control layers, including inflammatory signaling, antigen-presenting capacity, metabolic rewiring and resolution failure. This distinction reframes DC-driven immune rebalancing as a testable organizing framework: immunogenic DC functions may need to be enhanced when effector immunity is required, whereas tolerogenic or regulatory programs may need to be reinforced when inflammatory restraint is therapeutically desirable. By clarifying both the shared control layers and the disease-specific outputs of DC dysfunction, this review provides a balanced conceptual basis for future biomarker-guided and context-specific immunomodulatory strategies.