PD-L1 (Programmed Death-Ligand 1), also known as CD274, is a 40 kDa type 1 transmembrane protein that has been speculated to play a major role in suppressing the immune system during particular events such as pregnancy, tissue allografts, autoimmune disease, and cancer. In the nonneoplastic setting, PD-L1 is expressed on activated T cells, B cells, dendritic cells and macrophages, in addition to some immune-privileged nonhematopoietic tissues such as retina and placenta. Binding of PD-L1 to its ligand PD-1, which is expressed by various immune cell types including T cells, transmits an inhibitory signal that attenuates T cell function, expansion, and survival.
More recently, it has been discovered that the neoplastic cells of many human tumors can express PD-L1, including breast, ovarian, gastric, pancreatic, lung and renal cell carcinomas, and classical Hodgkin lymphoma (CHL). PD-L1 expression by tumor cells is thought to inhibit the local immune response to the tumor, at least in part by binding to T cell PD-1 and protecting the tumor from T-cell-mediated immunity.
Blockade of the PD-1/PD-L1 axis by humanized monoclonal antibodies against PD-1 and PD-L1 has emerged as a promising new cancer therapy. In recent clinical trials, anti-PD-1 therapy has been associated with significant clinical responses in patients with refractory non-hematopoietic tumors including melanoma, renal cell carcinoma, and non-small cell lung carcinoma (NSCLC), as well as CHL and diffuse large B cell lymphoma. As a result of these trials, the anti-PD-1 antibody nivolumab and pembrolizumab have received FDA approval for treating metastatic squamous NSCLC and metastatic melanoma, respectively.
PhenoPath scientists and pathologists are at the forefront in working with pharmaceutical companies looking for the features of the tumor which might predict response to these anti-PD-1 agents, particularly the expression of PD-L1 on the tumor cell population, as determined by immunohistochemistry. From these studies, we have optimized PD-1 and PD-L1 protocols, which have been analytically validated in our laboratory. While at the current time, no universally agreed-upon scoring system for PD-L1 exists, we are employing the same scoring system used in several of the clinical trials presented at the 2015 ASCO meeting, in which the percent of tumor cell positivity and the intensity are recorded.
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