CTLA4 and neoplasm: Since most CD8+ TIL express CTLA-4 early in tumor progression and Treg levels are reduced after CTLA-4 mAb treatment, both direct CD8+ TIL activation and Treg depletion may be one advantage of CTLA-4 blockade over blockade of the PD-axis, as evidence suggests that PD inhibition primarily reverses adaptive immune resistance only [28, 29].