Although the exact origin of sPD-L1 in cancer patients remains unclear, significant correlations, observed between increase of circulating sPD-L1 levels and fall of PD-L1 expression on both CD4+ (R2 = 0.937, p = 0.007) and CD8+ (R2 = 0.91, p = 0.012) T-cells in NIBIT-MESO-1 patients (Calabrò et al., manuscript in preparation), suggest that immune cell-surface expression of PD-L1 could be a source of the sPD-L1 detected in our cohort of patients. This evidence concerns the gene SPDL1 and cancer.