Fig. 5
From: IL-17A promotes tumorigenesis and upregulates PD-L1 expression in non-small cell lung cancer
IL-17A induced cellular oxidative stress and activated the Keap1/Nrf2/p62 pathway to block autophagy in NSCLC cells. IL-17A induced intracellular production of low levels of ROS. ROS caused a change in the link site between Keap1 and Nrf2, leading to the dissociation of Keap1 from Nrf2. The dissociated Nrf2 is transferred to the nucleus and binds with ARE to initiate antioxidant reactions. p62 competitively binds Keap1 to Nrf2. When Nrf2 was dissociated from Keap1, the combination of p62 and Keap1 increased, which could chelate Keap1 to autophagosomes. However, excessive accumulation of p62 can cause autophagy dysfunction, resulting in reduced degradation of substrates such as PD-L1 that are degraded through the autophagy pathway