We have recently demonstrated significantly increased systemic levels of the soluble variants of the co-inhibitory ICPs, CTLA-4, PD-1, and its ligand PD-L1, LAG-3, and TIM-3 (T-cell immunoglobulin and mucin domain-containing protein 3) in patients with BCC, a finding which is consistent with the involvement of these checkpoint proteins in promoting both systemic and intra-tumoral immune suppression in this malignancy [82]. This evidence concerns the gene CD274 and skin basal cell carcinoma.