The expression of programmed cell death protein 1 (PD-1)/programmed cell death protein 1 ligand (PD-L1) axis, cytotoxic T-lymphocyte antigen 4 (CTLA4), lymphocyte activation gene 3 (LAG3), T-cell immunoglobulin, and mucin domain-3 (TIM3) proteins on tumor cells limits the activation of the adaptive antitumor response, ultimately associated to an “exhausted” immune system that is unable to perform prolific cancer killing (Figure 1) [126,127]. The gene discussed is CD274; the disease is cancer.