If antigen-overexposure occurs, PD-1/PD-L1 signaling creates a positive feedback loop where this signaling becomes dominant and generates an exhausted T-cell population within the tumor and its periphery by inhibiting T-cell activation upon the recruitment of SHP2 tyrosine phosphatase which dephosphorylates CD28, attenuating TCR signaling [103]. The gene discussed is CD274; the disease is neoplasm.