Programmed death-ligand 1-derived peptide epitopes presented on HLA class I and class II molecules (PD-L1-derived HLA epitopes)

Programmed death-ligand 1 (PD-L1)-derived peptide epitopes presented on HLA class I and class II molecules are specific protein fragments used by the immune system to identify cells expressing the PD-L1 protein. While PD-L1 is primarily known as an immune checkpoint that inhibits T-cell activity by binding to PD-1, its intracellular degradation products are processed and displayed on the cell surface via the Major Histocompatibility Complex (MHC), also known as Human Leukocyte Antigen (HLA) in humans (Munir et al., 2013, Cancer Research). These peptide-MHC complexes serve as ligands for T-cell receptors (TCRs), enabling the immune system to recognize and eliminate cells that overexpress PD-L1 to evade immune detection. Therapeutic targeting of these epitopes, notably through cancer vaccines like IO103, aims to stimulate a robust immune response involving both cytotoxic CD8+ and helper CD4+ T cells (IO Biotech, 2024). This strategy is designed to directly kill tumor cells and deplete immunosuppressive regulatory cells, such as myeloid-derived suppressor cells (MDSCs), within the tumor microenvironment (ClinicalTrials.gov, NCT03806309). By converting a tumor's primary defense mechanism into a target for destruction, this approach offers a potential synergy with traditional checkpoint inhibitors to overcome therapeutic resistance.

Other names

PD-L1 epitopesCD274-derived HLA-presented peptidesPD-L1 MHC complexesIO103 target peptidesPD-L1-specific T-cell epitopes

Induction of specific cytotoxic CD8+ and helper CD4+ T-cell responses that recognize PD-L1-derived peptides presented on HLA molecules, leading to the direct lysis of PD-L1-expressing tumor cells and the depletion of immunosuppressive cells in the tumor microenvironment (Munir et al., 2013, Cancer Research; IO Biotech, 2024).