English: Figure 4  KEAP1/NRF2 modulation of antitumor immune responses. (a) Lung cancer patients with KEAP1-mutant tumors display signs of immune evasion with the exclusion of T cells. NRF2 activation by KEAP1 mutation may be selected for in lung cancer by enabling tumors to overcome metabolic bottlenecks [e.g., ROS (reactive oxygen species), hypoxia, nutrient availability] and suppress antitumor immune responses by altering the immune composition (e.g., T cells, myeloid cells, or other immune cell populations). Panel adapted with permission from Sayin et al. (2019). (b) Potential interactions of KEAP1-mutant cells with immune cell populations in the tumor microenvironment (TME). Metabolites secreted [e.g., lactate, GSH (glutathione)] or consumed (e.g., glucose, amino acids) by KEAP1-mutant tumors may alter the metabolic composition of the TME, therefore impacting the activity and function of effector T cells. In addition to a potential metabolism-dependent immune suppression, NRF2 transcriptionally regulates immunomodulatory pathways such as chemokines/cytokines (e.g., IL-1, -6, -11, -17d) and cGAS/STING-induced type I interferon (IFN).