Programmed cell death protein 1 (PD-1), also known as CD279, is a cell surface receptor protein encoded by the PDCD1 gene located on chromosome 2q37.3. PD-1 contains 288 amino acids with a molecular weight of around 55 kDa. Post-translational modifications of PD-1 include phosphorylation, glycosylation, and formation of disulfide bonds, which modulate its function and interactions with ligands. PD-1 is primarily categorized as a membrane protein, predominantly expressed on the surface of immune cells, particularly T cells.
The function of PD-1 is primarily immune regulation, serving as a key checkpoint receptor in the modulation of immune responses. PD-1 interacts with its ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2), expressed on antigen-presenting cells and other cell types. The binding of PD-1 to its ligands leads to the inhibition of T cell activation and effector functions, thereby suppressing immune responses and promoting immune tolerance. This mechanism helps prevent excessive immune activation and tissue damage, but it can also be exploited by cancer cells and pathogens to evade immune surveillance.
PD-1 expression is primarily observed in immune cells, including T cells, B cells, natural killer cells, and dendritic cells. It is particularly prominent in activated and exhausted T cells, where its expression is upregulated as a feedback mechanism to dampen excessive immune responses and maintain immune homeostasis. PD-1 expression can also be induced in response to inflammatory cytokines and other immune regulatory signals.
The expression of PD-1 is tightly regulated by various factors, including transcriptional regulators, cytokines, and signaling pathways involved in immune activation and tolerance. For example, transcription factors such as NFAT, AP-1, and NF-κB can modulate PDCD1 gene expression in response to T cell receptor signaling and cytokine stimulation. Additionally, inflammatory cytokines such as interferons can upregulate PD-1 expression as part of the immune response to infection or inflammation.
PD-1 and its dysregulation have been associated with various health conditions, diseases, and immune-related complications. In cancer, upregulation of PD-1 expression on tumor-infiltrating lymphocytes is a common mechanism of immune evasion, allowing cancer cells to evade immune surveillance and promote tumor growth. In infectious diseases, viruses may exploit the PD-1 pathway to evade immune responses and establish chronic infections. Additionally, dysregulation of PD-1 signaling has been implicated in autoimmune diseases, where excessive immune checkpoint inhibition can contribute to immune dysregulation and tissue damage.
Targeting PD-1 with monoclonal antibodies (mAbs) has emerged as a highly successful therapeutic strategy in oncology, leading to the development of immune checkpoint inhibitors (ICIs). Pembrolizumab (Keytruda) and nivolumab (Opdivo) are two notable examples of FDA-approved PD-1 inhibitors. These mAbs block and restore T cell activity, enhancing anti-tumor immune responses. These PD-1 inhibitors have demonstrated remarkable efficacy in various cancers, including melanoma, non-small cell lung cancer, and renal cell carcinoma, leading to durable responses and improved patient outcomes. Additionally, PD-1 inhibitors have been combined with other cancer therapies, such as chemotherapy, targeted therapy, and other immunotherapies, to enhance treatment efficacy.
Furthermore, PD-1 expression on immune cells can serve as a biomarker for disease prognosis and response to immunotherapy in certain cancers. High PD-1 expression on tumor-infiltrating lymphocytes is associated with a better response to PD-1 inhibitors and improved survival outcomes in some cancer patients. Conversely, PD-1 expression on immune cells in the tumor microenvironment may also indicate immune evasion and resistance to therapy in certain contexts, highlighting its importance as a prognostic marker and therapeutic target in cancer immunotherapy.
NeoBiotechologies offers a variety of antibodies against PD-1 that have been validated for ELISA, flow cytometry, immunofluorescence, immunohistochemistry, and Western blotting, as well as a HuProt validated option. Additionally, we hold exclusive rights to PD-1 antibodies available for licensing or collaboration [https://www.neobiotechnologies.com/shop/?s=PDCD1+%2F+PD1+%2F+CD279].
Synonyms
Programmed cell death protein 1, CD279; hPD-1; hSLE1; PD1; PDCD1; Programmed Cell Death Protein 1; Protein PD-1; SLEB2; Systemic lupus erythematosus susceptibility 2
Research Areas
Cardiovascular, Immunology, B Cell Markers, Infectious Disease, PD-1 blockade immunotherapy
