However, in the tumour environment, Tregs acquire a highly suppressive phenotype, termed tumour-infiltrating effector Treg cells, with increased expression of FOXP3 and CD25 (76) and upregulation of a variety of cell-surface molecules including CTLA-4, GITR, OX40, TIGIT, LAG-3, and TIM-3 (77), that is further enhanced by radiotherapy (78). This evidence concerns the gene TNFRSF4 and neoplasm.