Fig. 2: Implications of high NRF2 signaling in tumor and immune cells within the tumor microenvironment.
From: NRF2 immunobiology in cancer: implications for immunotherapy and therapeutic targeting
Tumor-intrinsic activation of NRF2 (left) leads to cellular reprogramming to promote immunoevasion and tumor resilience, including suppression of NF-κB signaling, downregulation of the STING pathway, expression of immunosuppressive ligands, and enhanced metabolic reprogramming. In the immune microenvironment (right), NRF2 signaling alters both myeloid and lymphoid compartments. Myeloid populations show expansion of CD11b⁺Gr1⁺ myeloid-derived suppressor cells (MDSCs), increased polarization of macrophages toward an M2-like phenotype, and reduced secretion of TNF-α, GM-CSF, and insulin by neutrophils. Lymphoid cells, particularly CD8 T cells, exhibit functional exhaustion with decreased IFN-γ and granzyme B expression. These microenvironmental changes collectively suppress pro-inflammatory cytokine production (IL-1, IL-6, IL-10, TNF-α, IFN-γ), and deplete essential nutrients such as amino acids (center).
