Demethylation by DNMTi (Aza) promoted acetylation of histone 3, and interaction with TIEG1 and Sp1, which ultimately led to upregulation of Foxp3. To study Tregs in non-small-cell lung cancer (NSCLC) using a co-culture system, Ke et al. showed demethylation of FOXP3 in the promoter region increased FOXP3 expression in Tregs, which led to downregulation of immune response in the TME (Figure 3) [100]. The gene discussed is SP1; the disease is non-small cell lung carcinoma.