The PD-L1 immunologic checkpoint

1. Inactive T cell
2. Tumor cell
3. PD-L1 on tumor-infiltrating immune cells can lead to inhibition of activated T cells
4. Activation of the PD-1 receptor by binding of PD-L1 causes inhibition of T cell signaling
5. PD-L1 binding to B7.1 on T cells and antigen-presenting cells can mediate down-regulation of immune responses
6. Constitutive immune resistance PD-L1 expression on tumor cells can be up-regulated by oncogenic signaling
7. Binding of the MHC antigen complex to the T cell receptor (TCR) triggers T cell signaling
8. Tumor cells up-regulate PD-L1 to evade immune-mediated destruction

PD-L1 is a transmembrane protein that down-regulates immune responses through binding to its two inhibitory receptors, programmed death-1 (PD-1) and B7.1. PD-1 is an inhibitory receptor expressed on T cells following T-cell activation, which is sustained in states of chronic stimulation such as in chronic infection or cancer.¹ Binding of PD-L1 with PD-1 inhibits T cell proliferation, cytokine production and cytolytic activity, leading to the functional inactivation or exhaustion of T cells. B7.1 is a molecule expressed on antigen presenting cells and activated T cells. PD-L1 binding to B7.1 on T cells and antigen presenting cells can mediate down-regulation of immune responses, including inhibition of T-cell activation and cytokine production.² PD-L1 expression has been observed in immune cells and tumor cells^3,4 of PD-L1 on tumor cells has been reported to impede anti-tumor immunity, resulting in immune evasion.¹ Therefore, interruption of the PD-L1/PD-1 pathway represents an attractive strategy to reinvigorate tumor-specific T cell immunity suppressed by the expression of PD-L1 in the tumor microenvironment.