PD-L1 is a diverse molecule regulating both tumor-intrinsic signaling and adaptive immunosuppression
Programmed death-ligand 1 (PD-L1) is a 33.28 kDa protein on the surface of many immune and non-immune cells (1-3). Its primary function as a co-stimulatory molecule is well documented (4). PD-L1 serves as an ‘immune checkpoint’ and it binds to receptor programmed death-1 (PD-1) to regulate immune responses among antigen presenting cells and T-cells. Unfortunately, this exact mechanism is exploited by tumor cells where increased expression of PD-L1 results in immunosuppression of the adaptive tumor response by inhibiting T-cell proliferation, reducing T-cell survival, inhibiting cytokine release, and promoting T-cell apoptosis (5,6). This leads to T-cell exhaustion and immunosuppression in the tumor microenvironment (7).