Structure of PD-1

Programmed Cell Death Protein 1 (PD-1) is a type I transmembrane protein belonging to the CD28 family of immune checkpoint receptors. It consists of:

Extracellular domain: A single IgV-like domain responsible for binding to its ligands (PD-L1 and PD-L2).

Transmembrane region: Anchors PD-1 in the T cell membrane.

Cytoplasmic tail: Contains two key motifs—Immunoreceptor Tyrosine-Based Inhibitory Motif (ITIM) and Immunoreceptor Tyrosine-Based Switch Motif (ITSM)—which regulate downstream inhibitory signaling.

Function of PD-1

PD-1 is an immune checkpoint receptor that downregulates T-cell activity, preventing excessive immune responses and maintaining immune tolerance. It plays a crucial role in:

Immune homeostasis: Prevents autoimmunity by suppressing self-reactive T cells.

Cancer immune evasion: Tumors exploit PD-1 signaling to escape immune detection.

Infectious diseases: Chronic infections upregulate PD-1, leading to T-cell exhaustion.

PD-1 Signaling Pathway

Ligand Binding: PD-1 binds to PD-L1 (expressed on tumor and immune cells) or PD-L2 (mainly on antigen-presenting cells).

Tyrosine Phosphorylation: Ligand binding activates ITIM and ITSM motifs.

Recruitment of SHP-2: The phosphatase SHP-2 is recruited, dephosphorylating key signaling molecules.

T-cell Inhibition: This leads to decreased activation of PI3K-AKT, Ras-MEK-ERK, and ZAP70 pathways, reducing cytokine production and T-cell proliferation.

Market Prospects of PD-1 Inhibitors

The global PD-1/PD-L1 inhibitor market was valued at $37.7 billion in 2022 and is expected to exceed $80 billion by 2030 due to increasing cancer incidence.

Combination therapies (PD-1 inhibitors with chemotherapy, radiotherapy, or other checkpoint inhibitors) are expanding indications beyond oncology to autoimmune diseases.

FDA-Approved PD-1 Inhibitors

PD-1 inhibitors continue to dominate immuno-oncology, with ongoing research expanding their use in infectious diseases and autoimmune disorders.

Our PD-1/PD-L1 Related Antibody Products