A new tool in the cancer immunotherapy toolbox?

Programmed cell death-1 (PD-1), a member of the CD28 superfamily, is primarily expressed on the surface of T cells. The normal function of PD-1 is to dampen the immune activity and promote self-tolerance of activated CD8⁺ cytotoxic T cells by suppressing T cell inflammatory reactions. Binding of PD-1 with its ligand PD-L1 (or B7-H1) or PD-L2 (or B7-DC) excessively leads to the exhaustion of CD8⁺ cytotoxic T cells (1). In most of patients with advanced cancers, CD8⁺ cytotoxic T cells are exhausted owing to the engagement of PD-1 by the aberrantly expressed PD-L1 on tumor cells and/or nurse cells in the tumor microenvironment.