Cluster of differentiation refers to an attempt to catalogue systematically a series of over 300 cell-surface proteins associated with immunotyping. Many members of the group have identified functions as enzymes (for example, see CD73 ecto-5'-nucleotidase) or receptors (for example, see CD41 integrin, alpha 2b subunit). Many CDs are targeted for therapeutic gain using antibodies for the treatment of proliferative disorders. A full listing of all the Clusters of Differentiation proteins is not possible in the Guide to PHARMACOLOGY; listed herein are selected members of the family targeted for therapeutic gain.

The endogenous ligands for human PD-1 are programmed cell death 1 ligand 1 (CD274, Q9NZQ7) (PD-L1 aka CD274) and programmed cell death 1 ligand 2 (PD-L2; PDCD1LG2). These ligands are cell surface peptides, normally involved in immune system regulation. Expression of PD-1 by cancer cells induces immune tolerance and evasion of immune system attack [20]. Anti-PD-1 monoclonal antibodies are used to induce immune checkpoint blockade as a therapeutic intervention in cancer, effectively re-establishing immune vigilance. Pembrolizumab was the first anti-PD-1 antibody to be approved by the US FDA.

* Key recommended reading is highlighted with an asterisk

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* Chi Z, Lu Y, Yang Y, Li B, Lu P. (2021) Transcriptional and epigenetic regulation of PD-1 expression. Cell Mol Life Sci, 78 (7): 3239-3246. [PMID:33738533]

* Gabius HJ, Kaltner H, Kopitz J, André S. (2015) The glycobiology of the CD system: a dictionary for translating marker designations into glycan/lectin structure and function. Trends Biochem Sci, 40 (7): 360-76. [PMID:25981696]

* Huang MY, Jiang XM, Wang BL, Sun Y, Lu JJ. (2021) Combination therapy with PD-1/PD-L1 blockade in non-small cell lung cancer: strategies and mechanisms. Pharmacol Ther, 219: 107694. [PMID:32980443]

* Peng Z, Li M, Li H, Gao Q. (2023) PD-1/PD-L1 immune checkpoint blockade in ovarian cancer: Dilemmas and opportunities. Drug Discov Today, 28 (8): 103666. [PMID:37302543]

* Vosoughi T, Bagheri M, Hosseinzadeh M, Ehsanpour A, Davari N, Saki N. (2019) CD markers variations in chronic lymphocytic leukemia: New insights into prognosis. J Cell Physiol, 234 (11): 19420-19439. [PMID:31049958]

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