CD137

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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
Ensembl
UniProt
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: 150.91 – 150.95 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.

Expression[edit]

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[edit]

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[edit]

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

As a drug target[edit]

Utomilumab[edit]

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[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000049249 - Ensembl, May 2017
  2. ^ a b c 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. ^ a b 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

External links[edit]

Further reading[edit]