CTLA4 and colorectal cancer: Several clinical studies such as Austrian Breast and Colorectal Cancer Study Group trial 12 (ABCSG-12), Zometa-Femara Adjuvant Synergy Trial (ZO-FAST), and Adjuvant Zoledronic acid to reduce recurrence (AZURE) studies demonstrated modulation of immune-suppressing regulatory T (Treg) cells by inhibiting its proliferative capacity via downregulating CCR4, PD-1, CTLA-4 and cells the immunomodulatory effects of Zol by receptor activator of nuclear factor kappa-B ligand (RANKL) on Treg cells.51