Programmed cell death 1 receptor (PD-1) (PD-1)

Programmed cell death 1 (PD-1), encoded by the PDCD1 gene, is a critical immune checkpoint receptor expressed on the surface of activated T cells, B cells, and myeloid cells (UniProt Q15116). Its primary biological role is to downregulate immune responses and promote self-tolerance by interacting with its ligands, PD-L1 and PD-L2, which are frequently upregulated by tumor cells to evade immune surveillance (PubMed: 17502820). This interaction triggers inhibitory signaling that leads to T-cell exhaustion, characterized by reduced proliferation and cytokine production. In advanced immunotherapy, the PDCD1 gene in autologous tumor-infiltrating lymphocytes (TILs) is a target for genetic modification, such as CRISPR-Cas9 mediated knockout, to create 'exhaustion-resistant' T cells (PubMed: 32337501). By eliminating the PD-1 receptor, these engineered TILs can maintain their anti-tumor activity even in the presence of inhibitory ligands, offering a potent strategy for treating refractory solid tumors (NIH/NCI). This approach combines the specificity of adoptive cell transfer with the power of checkpoint blockade at the cellular level.

Other names

PDCD1CD279Programmed cell death protein 1SLEB2hPD-1

PD-1 acts as an inhibitory checkpoint receptor that recruits the phosphatase SHP-2 to its cytoplasmic tail upon binding to ligands PD-L1 or PD-L2, leading to the dephosphorylation of T-cell receptor (TCR) signaling molecules and the suppression of T-cell activation (UniProt Q15116). In the specific context of autologous tumor-infiltrating lymphocytes (TILs), the PDCD1 gene is targeted for genetic knockout or silencing to prevent this inhibitory signaling, thereby protecting the T cells from exhaustion and maintaining their cytotoxic efficacy within the immunosuppressive tumor microenvironment (PubMed: 32337501).