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Programmed cell death protein 1 receptor (PD‑1), also known as cluster of differentiation 279 (CD279), is an inhibitory immune checkpoint receptor expressed on activated T cells—including subsets of cytotoxic CD8-positive lymphocytes—and B cells. Its primary function is to down-regulate immune responses by inhibiting signaling through the antigen-specific T-cell receptor and suppressing costimulatory molecules like CD28. This mechanism promotes self-tolerance and prevents autoimmunity but can also be exploited by tumors to evade immune surveillance. In chronic infections and malignancies, high levels of PD‑1 are found on “exhausted” or dysfunctional memory-type tissue-resident memory CD8-positive lymphocytes. Therapeutic antibodies targeting this pathway—such as pembrolizumab and nivolumab—block the interaction between PD‑L1/PD-L2 ligands on tumor or other cells with PD‑1 on these lymphocytes, thereby restoring their ability to attack cancerous tissues. The presence or induction level of these receptors serves both as a biomarker for therapy selection and a target for immunomodulatory drugs; however, blockade can lead to significant autoimmune side effects due to loss of normal inhibitory control over self-reactive lymphocytes.
Blockade of the PD‑1/PD-L1 interaction to restore/enhance antitumor immune responses by reactivating exhausted or suppressed cytotoxic CD8+ T cells
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