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PD-L1 binds to its receptor, PD-1, found on activated T cells, B cells, and myeloid cells, to modulate activation or inhibition. The affinity between PD-L1 and PD-1, as defined by the dissociation constant K d, is 770 nM. PD-L1 also has an appreciable affinity for the costimulatory molecule CD80 (B7-1), but not CD86 (B7-2). [11]
In the cancer disease state, the interaction of PD-L1 on the tumor cells with PD-1 on a T-cell reduces T-cell function signals to prevent the immune system from attacking the tumor cells. [9] Use of an inhibitor that blocks the interaction of PD-L1 with the PD-1 receptor can prevent the cancer from evading the immune system in this way. [ 9 ]
The expression of PD-L1 (programmed death-ligand 1; one of the immune checkpoints) has been demonstrated to be a good biomarker of PD-L1 blockade therapy in some cancers. [10] However, there is a need for better biomarkers as there are some predictive errors with PD-L1 expression. [10]
Programmed cell death protein 1 (PD-1), (CD279 cluster of differentiation 279). PD-1 is a protein encoded in humans by the PDCD1 gene. [5] [6] PD-1 is a cell surface receptor on T cells and B cells that has a role in regulating the immune system's response to the cells of the human body by down-regulating the immune system and promoting self-tolerance by suppressing T cell inflammatory activity.
Tumor cells express PD-L1 in high amounts which prevents T cells from attacking them. Another mechanism that cancer cells use is the downregulation of MHC I. Major histocompatibility complex class I (MHC I) molecules are expressed on cell surfaces with the role of alerting the immune system to the presence of infected cells.
A prognostic biomarker provides information about the patients overall outcome, regardless of any treatment or therapeutic intervention. [6] One example of a prognostic biomarkers in clinical research, is the use of mutated PIK3CA in the study of metastatic breast cancer.
In cancer research and medicine, biomarkers are used in three primary ways: [19] To help diagnose conditions, as in the case of identifying early stage cancers (diagnostic) To forecast how aggressive a condition is, as in the case of determining a patient's ability to fare in the absence of treatment (prognostic)
Among PD-L1 functions is a key regulatory role on T cell activities. It appears that (cancer-mediated) upregulation of PD-L1 on the cell surface may inhibit T cells that might otherwise attack. PD-L1 on cancer cells also inhibits FAS- and interferon-dependent apoptosis, protecting cells from cytotoxic molecules produced by T cells.