Fig. 1.

PD-L1-specific T cells target immune regulatory cells as well as cancer cells. Cancer cells (purple) as well as other regulatory immune cells [e.g., tumor-associated dendritic cells (TADC) (dark red) and MDSC (light red)] express checkpoint inhibitors (e.g., PD-L1), inhibitory cytokines as well as metabolic enzymes that restrain the antitumor activity of anti-tumor-specific T cells (green) in the tumor microenvironment. Specific T cells recognizing HLA-restricted PD-L1-derived epitopes (yellow), which are generated from intracellular degraded PD-L1, are able to eliminate (red arrows) regulatory immune cells as well as cancer cells. Hence, the activation of PD-L1-specific T cells by vaccination may directly target immune inhibitory pathways in the tumor microenvironment, modulate immune regulation, and potentially alter tolerance to tumor antigens. The addition of PD-L1 epitopes to therapeutic cancer vaccines would thus be a simple and highly synergistic means to increase the outcome