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Tumor cells can escape the immune surveillance and disrupt immune checkpoint of host in several methods, therefore, to avoid the elimination from the host immune system. Numerous pathways are utilized by cancers to up-regulate the negative signals through cell surface molecules, thus inhibit T-cell activation or induce apoptosis and promote the progression and metastasis of cancers . Immunotherapeutic approaches utilizing antagonistic antibodies to block checkpoint pathways, can release cancer inhibition and facilitate antitumor activity, so as to achieve the purpose of treating cancer.
The present research of immune checkpoint molecules is mainly focus on cytotoxic T lymphocyte-associated antigen 4 (CLTA-4), Programmed death-1 (PD-1) and its ligands PD-L1 (B7H1) and PD-L2 (B7-DC). PD-1 and its ligands have been rapidly established as the currently most important breakthrough targets in the development of effective immunotherapy.
What is the PD-1/PD-L1 pathway?
The PD-1 (programmed cell death-1) receptor is expressed on the surface of activated T cells. Its ligands, PD-L1 and PD-L2, are commonly expressed on the surface of dendritic cells or macrophages. PD-1 and PD-L1/PD-L2 belong to the family of immune checkpoint proteins that act as co-inhibitory factors, which is known to drive T cell dysfunction. In response to immune attack, cancer cells overexpress PD-L1 and PD-L2. They bind to PD-1 receptor on T cells, inhibiting the activation of T-cells, thus suppressing T-cell attack and inducing tumor immune escape. High-affinity anti-PD-1 or anti-PD-L1 monoclonal antibodies (mAbs), which block PD-1–PD-L1 interaction, can reverse the immune checkpoint.
The role of PD-1/PD-L1 in cancer
Under normal conditions, the immune system performs a series of steps which lead to an anticancer immune response and cancer cell death, known as the cancer immunity cycle1:
PD-1/PD-L1 pathway regulates immune suppression by multiple mechanisms
Immune checkpoints are proteins which can turn up or turn down signals in the immune system. Inhibitors of immune-checkpoint proteins have been considered as new targets for cancer immunotherapies. To accelerate research progress of PD-1/PD-L1 pathway, we have developed a variety of PD-1/PD-L1 pathway-product panels including stable cell lines, viral particles and clones.