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PDCD1

Monday 3 June 2013

PD-1; CD279; programmed death-1 (PD-1)

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Programmed cell death protein 1 also known as PD-1 is a protein that in humans is encoded by the PDCD1 gene.

PDCD1 has also been designated as CD279 (cluster of differentiation 279). This gene encodes a cell surface membrane protein of the immunoglobulin superfamily.

This protein is expressed in pro-B cells and is thought to play a role in their differentiation.

Diagnostic use

- T-cell lymphomas

  • Peripheral T-cell lymphomas are a heterogeneous group that often requires the use of ancillary testing for accurate diagnosis.
  • This is particularly applicable to the diagnosis of angiommunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, unclassified (PTCLU), because of their histologic and immunophenotypic overlap with reactive lymphoid proliferations.
  • Immunohistochemistry for programmed death-1 (PD-1), a marker of follicular helper T cells, was shown to be sensitive in the detection of angiommunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, unclassified (PTCLU).

- reactive lymphadenopathies (20087161)

  • The majority of reactive lymphadenopathies including Cat-scratch disease, Kikuchi lymphadenitis, Castleman disease, and reactive follicular hyperplasia show no PD-1 staining outside follicles. (20087161)
  • Some reactive lymph nodes, show increased extrafollicular PD-1-positive cells in a pattern similar to AITL and PTCLU, and include progressive transformation of germinal centers, viral lymphadenitis (Epstein-Barr virusand human immunodeficiency virus) and Rosai-Dorfman disease. (20087161)
  • PD-1-positive cells may be increased in a number of settings other than T-cell lymphomas. (20087161)
  • Staining for PD-1 in reactive and atypical lymphadenopathies should be interpreted with caution and in the context of other ancillary immunophenotypic and molecular studies before a diagnosis of AITL or PTCLU is entertained. (20087161)

Targeted therapy

Monoclonal antibodies targeting PD-1 that boost the immune system are being developed for the treatment of cancer.

- nivolumab

  • nivolumab produced complete or partial responses in non-small-cell lung cancer, melanoma, and renal-cell cance. Colon and pancreatic cancer did not have a response.

- lambrolizumab

  • Lambrolizumab (also known as MK-3475) is a drug in development by Merck that targets the PD-1 receptor.
  • The drug is intended for use in treating metastatic melanoma.

See also

- PDCDs

References

- PD-1 expression in T-cell lymphomas and reactive lymphoid entities: potential overlap in staining patterns between lymphoma and viral lymphadenitis. Krishnan C, Warnke RA, Arber DA, Natkunam Y. Am J Surg Pathol. 2010 Feb;34(2):178-89. doi : 10.1097/PAS.0b013e3181cc7e79 PMID: 20087161 [Free]