Small molecule PD-L1 inhibitor modulates expression of PD-L1 on the cell surface – a potential mechanism of blocking interaction with PD-1

Small-molecule inhibitors of PD-1/PD-L1 immune checkpoint alleviate the PD-L1-induced exhaustion of T-cells

Antibodies targeting the PD-1/PD-L1 immune checkpoint achieved spectacular success in anticancer therapy in the recent years. In contrast, no small molecules with cellular activity have been reported so far. Here we provide evidence that small molecules are capable of alleviating the PD-1/PD-L1 immune checkpoint-mediated exhaustion of Jurkat T-lymphocytes. The two optimized small-molecule inhib...

Regulation of PD-1/PD-L1 pathway and resistance to PD-1/PD-L1 blockade

Immune checkpoint blockades, such as inhibitors against programmed death 1 (PD-1) and its ligand (PD-L1), have received extensive attention in the past decade because of their dramatic clinical outcomes in advanced malignancies. However, both primary and acquired resistance becomes one of the major obstacles, which greatly limits the long-lasting effects and wide application of PD-1/PD-L1 block...

Macrophage PD-L1 strikes back: PD-1/PD-L1 interaction drives macrophages toward regulatory subsets

Activated macrophages have been simply defined as cells that secrete inflammatory mediators and kill intracellular pathogens until few years ago. Recent studies have proposed a new classification system to separate activated macrophages based on their functional phenotypes: host defense, wound healing, and immune regulation. Regulatory macrophages can arise following innate or adaptive immune r...

Over-Expression of Immunosuppressive Molecules, PD-L1 and PD-L2, in Ulcerative Colitis Patients

Blocking the PD-1/PD-L1 pathway in glioma: a potential new treatment strategy

Gliomas are the most common type of primary brain tumor in adults. High-grade neoplasms are associated with poor prognoses, whereas low-grade neoplasms are associated with 5-year overall survival rates of approximately 85%. Despite considerable progress in treatment modalities, the outcomes remain dismal. As is the case with many other tumors, gliomas express or secrete several immunosuppressiv...