The exact mechanism by which anti-CTLA-4 mediates enhanced anti-tumor reactivity is not clear, but may involve a combination of effects involving the lowering of the threshold needed to activate T-cells, a reduction in the number of Tregs, the reduced release of the suppressive factor indoleamine 2,3-dioxygenase (IDO) as well as broadening the peripheral T-cell receptor repertoire (47, 48). This evidence concerns the gene CTLA4 and neoplasm.