Nevertheless, a few reports have demonstrated decreases in intratumoral Tregs during immunotherapy; for example, Liakou et al. reported that bladder cancer tissue from patients treated with anti-CTLA-4 mAb (ipilimumab) became infiltrated with IFN-γ-producing Teff cells while CD4+Foxp3+ Treg numbers dwindled; however, the mechanism underlying this Treg reduction was not elucidated33. This evidence concerns the gene CTLA4 and urinary bladder carcinoma.