CD137

CD137 is a member of the tumor necrosis factor (TNF) receptor family. Its alternative names are tumor necrosis factor receptor superfamily member 9 (TNFRSF9), 4-1BB and induced by lymphocyte activation (ILA). It is of interest to immunologists as a co-stimulatory immune checkpoint molecule.

TNFRSF9
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTNFRSF9, 4-1BB, CD137, CDw137, ILA, tumor necrosis factor receptor superfamily member 9, TNF receptor superfamily member 9
External IDsOMIM: 602250 MGI: 1101059 HomoloGene: 1199 GeneCards: TNFRSF9
Orthologs
SpeciesHumanMouse
Entrez

3604

21942

Ensembl

ENSG00000049249

ENSMUSG00000028965

UniProt

Q07011

P20334

RefSeq (mRNA)

NM_001561

NM_001077508
NM_001077509
NM_011612

RefSeq (protein)

NP_001552

NP_001070976
NP_001070977
NP_035742

Location (UCSC)Chr 1: 7.92 – 7.94 MbChr 4: 151 – 151.03 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Expression

CD137 is expressed by activated T cells of both the CD4+ and CD8+ lineages.[5] Although it is thought to function mainly in co-stimulating those cell types to support their activation by antigen presenting cells expressing its ligand (CD137L), CD137 is also expressed on dendritic cells, B cells, NK cells, neutrophils and macrophages.[6]

Specific effects on cells

The best characterized activity of CD137 is its costimulatory activity for activated T cells. Crosslinking of CD137 enhances T cell proliferation, IL-2 secretion, survival and cytolytic activity. Further, it can enhance immune activity to eliminate tumors in mice.

Interactions

CD137 has been shown to interact with TRAF2.[7][8]

As a drug target

Utomilumab

Utomilumab (PF-05082566) targets this receptor to stimulate a more intense immune system attack on cancers.[9] It is a fully human IgG2 monoclonal antibody.[10] It is in early clinical trials.[9] As of June 2016 5 clinical trials are active.[11]

See also

References

  1. GRCh38: Ensembl release 89: ENSG00000049249 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000028965 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Wehler TC, Karg M, Distler E, Konur A, Nonn M, Meyer RG, et al. (November 2008). "Rapid identification and sorting of viable virus-reactive CD4(+) and CD8(+) T cells based on antigen-triggered CD137 expression". Journal of Immunological Methods. 339 (1): 23–37. doi:10.1016/j.jim.2008.07.017. PMID 18760281.
  6. Vinay DS, Kwon BS (July 2011). "4-1BB signaling beyond T cells". Cellular & Molecular Immunology. 8 (4): 281–4. doi:10.1038/cmi.2010.82. PMC 4002439. PMID 21217771.
  7. Jang IK, Lee ZH, Kim YJ, Kim SH, Kwon BS (January 1998). "Human 4-1BB (CD137) signals are mediated by TRAF2 and activate nuclear factor-kappa B". Biochemical and Biophysical Research Communications. 242 (3): 613–20. doi:10.1006/bbrc.1997.8016. PMID 9464265.
  8. Arch RH, Thompson CB (January 1998). "4-1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth factor receptor subfamily that bind TNF receptor-associated factors and activate nuclear factor kappaB". Molecular and Cellular Biology. 18 (1): 558–65. doi:10.1128/MCB.18.1.558. PMC 121523. PMID 9418902.
  9. Pfizer cancer drug shows promise in combo with Merck's Keytruda. May 2016
  10. Phase 1 Study of Utomilumab (PF-05082566) In Combination with Rituximab in Patients with CD20+ NHL (Study B1641001)
  11. PF-05082566 trials
  • Human TNFRSF9 genome location and TNFRSF9 gene details page in the UCSC Genome Browser.

Further reading

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