NRF2 immunobiology in cancer: implications for immunotherapy and therapeutic targeting
Harit Panda, Natalie G. Rowland, Caroline M. Krall, Brittany M. Bowman, Michael B. Major, Paul Zolkind
Abstract
Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that acts as a key regulator in cellular defense mechanisms against oxidative stress and xenobiotics. NRF2 modulates the expression of over 200 genes involved in antioxidant response, drug metabolism, and cellular resilience. Constitutive activation of NRF2 is a common event in cancer and recent advances provide remarkable insights into the role of NRF2 in oncogenesis, immune evasion, and treatment resistance.
Key Findings
- NRF2 modulates over 200 genes involved in antioxidant response and drug metabolism
- Constitutive NRF2 activation promotes oncogenesis, immune evasion, and treatment resistance
- NRF2 activation is associated with impaired responses to anti-PD1 immunotherapy
- Heme-driven NRF2 activation in tumor-associated macrophages drives immunosuppressive phenotype
Clinical Significance
Comprehensive review establishing NRF2 as a critical determinant of immunotherapy response. Directly relevant to predicting which cancer patients will respond to checkpoint inhibitors.
Citation
Panda, H. et al. (2025). NRF2 immunobiology in cancer. Oncogene.