Programmed cell death 1

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Programmed cell death 1, abbreviated PDCD1 and PD1,[1] is a protein (and gene) with an important role in immune system regulation and cancer. It is found on T lymphocytes.

It is also known as CD279.

PD1 binds with programmed death-ligand 1 (dealt with separately) and programmed death-ligand 2.[2]

Background

Cytotoxic T cell function is regulated by receptor pairs found on the tumour and lymphocyte:[2]

Function Tumour cell T cell
Antigen presentation MHC TCR
Signal inhibition PD-1 PD-L1 (CD274), PD-L2 (CD273)

Drugs

  • Pembrolizumab.
  • Nivolumab.
  • Atezolizumab.
  • Durvalumab.
  • Avelumab.

Uncertain whether it binds PD-1:

  • Pidilizumab.

IHC

  • There is no standard antibody.
  • Currently, each drug company has its own clone. Whether the antibodies are interchangeable is a subject of study.
Clone Associated drug Testing required
28-8 Nivolumab[3] no testing for squamous carcinoma, pending further information for non-squamous
22C3 Pembrolizumab[4] testing required
SP142 Atezolizumab[5] testing required
SP263 Durvalumab testing likely required

See also

References

  1. Online 'Mendelian Inheritance in Man' (OMIM) 600244
  2. 2.0 2.1 Ribas, A. (Jun 2012). "Tumor immunotherapy directed at PD-1.". N Engl J Med 366 (26): 2517-9. doi:10.1056/NEJMe1205943. PMID 22658126.
  3. Borghaei, H.; Paz-Ares, L.; Horn, L.; Spigel, DR.; Steins, M.; Ready, NE.; Chow, LQ.; Vokes, EE. et al. (Oct 2015). "Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer.". N Engl J Med 373 (17): 1627-39. doi:10.1056/NEJMoa1507643. PMID 26412456.
  4. Garon, EB.; Rizvi, NA.; Hui, R.; Leighl, N.; Balmanoukian, AS.; Eder, JP.; Patnaik, A.; Aggarwal, C. et al. (May 2015). "Pembrolizumab for the treatment of non-small-cell lung cancer.". N Engl J Med 372 (21): 2018-28. doi:10.1056/NEJMoa1501824. PMID 25891174.
  5. Fehrenbacher, L.; Spira, A.; Ballinger, M.; Kowanetz, M.; Vansteenkiste, J.; Mazieres, J.; Park, K.; Smith, D. et al. (Apr 2016). "Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial.". Lancet 387 (10030): 1837-46. doi:10.1016/S0140-6736(16)00587-0. PMID 26970723.