“…Treg-mediated immunosuppression has been targeted to enhance the efficacy of natural or induced antitumoral immunity mainly in preclinical models of GBM. This includes depletion of Treg by anti-CD25 antibodies ( 145 , 222 , 226 , 227 ), interference with their immunosuppressive activity, e.g., by blocking surface molecules such as CTLA-4 ( 222 , 228 , 229 ), TIGIT ( 230 ), Tim-3 ( 231 ), and PD-1 ( 229 , 230 , 232 ) or enzymes like ecto-5′-nucleotidase (CD73) ( 233 ) and IDO ( 229 ), or by preventing the accumulation of Treg in the TME by blocking CCR4-mediated migration ( 225 ). Irrespective of the approach, these studies could document a beneficial effect, with increased survival and reduction of tumor burden associated with restoration of antitumoral immunity, particularly when different strategies were combined.…”