Background: There are numerous checkpoint receptors; however, the most well-known is programmed cell death protein 1 (PD-1) and its ligand (PD-L1). Physiologically, checkpoint inhibitors mediate immune tolerance as a protective control measure during inflammation. In the case of PD-1/PD-L1, PD-1 is found on T and B cells, and is upregulated in response to stimulation. When these T and B cells come into contact with other cells expressing the matching ligand PD-L1, the T and B cells are tolerized and pro-inflammatory responses are suppressed. In cancer, tumor cells express an abundance of PD-L1 and effectively prevent the normal T-cell killing response. Treatment with inhibitors (usually monoclonal antibodies) that bind and block these surface receptors and ligands prevent immune tolerance and favors pro-inflammatory responses which help to overcome immune tolerance.
Principle: In this assay, stimulated lymphocytes are cultured for several days in the presence of a checkpoint inhibitor or other immunomodulatory article. Lymphocyte responses (proliferation, activation, cytokines, etc.) are measured and used to assess change caused by therapeutic intervention.