NFE2L2 and cancer: While NRF2 protects macrophages against oxidative insults, it concurrently impairs their antitumor capacity, diverting them from pro-inflammatory functions to an immunosuppressive state.10, 13 In hemorrhagic tumor areas, for example, TAMs encountering damaged red blood cells and heme upregulate NRF2-responsive genes, biasing them toward procancerous phenotypes.514, 17 Consequently, macrophage-based stress resilience through NRF2 may inadvertently fuel immunosuppressive TAM states, advancing cancer progression and undermining immunotherapies.