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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 ]
A tumor marker is a biomarker that can be used to indicate the presence of cancer or the behavior of cancers (measure progression or response to therapy). They can be found in bodily fluids or tissue.
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.
Triple-negative breast cancer comprises 15–20% of all breast cancer cases [3] and affects more young women or women with a mutation in the BRCA1 gene than other breast cancers. [4] Triple-negative breast cancers comprise a very heterogeneous group of cancers. TNBC is the most challenging breast cancer type to treat. [5]
A cancer biomarker refers to a substance or process that is indicative of the presence of cancer in the body. A biomarker may be a molecule secreted by a tumor or a specific response of the body to the presence of cancer.