Basis of PD1/PD-L1 Therapies

It is obvious that tumor cells have developed a number of strategies to escape immune surveillance including an altered expression of various immune checkpoints, such as the programmed death-1 receptor (PD-1) and its ligands PD-L1 and PD-L2. The interaction between PD-1 and PD-L1 results in an activation of self-tolerance pathways in both immune cells as well as tumor cells. Thus, these molecules represent excellent targets for T cell-based immunotherapies. However, the efficacy of therapies using checkpoint inhibitors is variable and only a limited number of patients receive a long-term response, while others develop resistances. Therefore, a better insight into the constitutive expression levels and their control as well as the predictive and prognostic value of PD-1/PD-L1, which are controversially discussed due to the methodological assessment, the dynamic and time-related variable expression of these molecules, is urgently required. In this review, the current knowledge of the PD-L1 and PD-1 genes, their expression in immune and tumor cells, the underlying molecular mechanisms of their regulation and their association with clinical parameters and therapy responses are summarized.