IL18 and neoplasm: Given that the cg05687149 sites was hypermethylated in RCC tumor (Fig. 2A–C), which was also not related to IL18 expression (Fig. 4A) but associated with the immune cell infiltration and immune suppressive microenvironment in RCC (Figs. 7A, E and 8A, G), we proposed that CpG sites located in different regions of IL18 promoter might be bound by different regulator such as transcription factors and chromatin remodelers, which could affect the expression of IL18 and its biological functions.