CTLA4 and nonpapillary renal cell carcinoma: Moreover, CTLA4 promoter methylation and its mRNA expression showed a significant association with the composition of the ccRCC tumor microenvironment: CTLA4 overexpression and concomitant promoter hypomethylation were associated with particularly high lymphocyte infiltration and an increased interferon-γ signature as well as cytolytic activity.