This is exemplified in an adoptive transfer experiment using CAR-T cells (Moon et al., 2014): in the tumor microenvironment, CAR-T cells rapidly became hypofunctional with identified upregulation of intrinsic T-cell inhibitory enzymes (DGK-α, DGK-ζ, SHP-1) as well as expression of surface co-inhibitory receptors (PD-1, LAG-3, TIM-3, 2B4). Here, DGKZ is linked to neoplasm.