View source for CD137

{{Infobox_gene}}
'''CD137''' is a member of the tumor necrosis factor ([[Tumor necrosis factors|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 currently of interest to immunologists as a co-stimulatory [[immune checkpoint]] molecule.

==Expression==

CD137 can be expressed by activated [[T cells]], but to a larger extent on [[CD8]] than on [[CD4]] [[T cells]]. In addition, CD137 expression is found on [[dendritic cells]], B cells, follicular dendritic cells, natural killer cells, granulocytes and cells of blood vessel walls at sites of [[inflammation]].

==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 [[Protein-protein interaction|interact]] with [[TRAF2]].<ref name=pmid9464265>{{cite journal | vauthors = Jang IK, Lee ZH, Kim YJ, Kim SH, Kwon BS | title = Human 4-1BB (CD137) signals are mediated by TRAF2 and activate nuclear factor-kappa B | journal = Biochem. Biophys. Res. Commun. | volume = 242 | issue = 3 | pages = 613–20 | date = Jan 1998 | pmid = 9464265 | doi = 10.1006/bbrc.1997.8016 }}</ref><ref name=pmid9418902>{{cite journal | vauthors = Arch RH, Thompson CB | title = 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 | journal = Mol. Cell. Biol. | volume = 18 | issue = 1 | pages = 558–65 | date = Jan 1998 | pmid = 9418902 | pmc = 121523 }}</ref>

==As a drug target==
===Utomilumab===
[[Utomilumab]] (PF-05082566) targets this receptor to stimulate a more intense immune system attack on cancers.<ref name=Pfizer2016-05>[https://www.reuters.com/article/us-health-cancer-pfizer-immunotherapy-idUSKCN0Y92W2 Pfizer cancer drug shows promise in combo with Merck's Keytruda. May 2016]</ref> It is a fully human IgG2 monoclonal antibody.<ref>[http://www.ercongressi.it/slides-NDH-Carlton/10-05/A-Thall.pdf Phase 1 Study of Utomilumab (PF-05082566) In Combination with Rituximab in Patients with CD20+ NHL (Study B1641001)]</ref> It is in early clinical trials.<ref name=Pfizer2016-05/> {{as of |2016|6}} 5 clinical trials are active.<ref>[https://clinicaltrials.gov/ct2/results?term=PF-05082566&Search=Search PF-05082566 trials]</ref>

== See also ==
* [[4-1BB ligand]]
* [[Urelumab]]

== References ==
{{Reflist}}

==External links==
* {{UCSC gene info|TNFRSF9}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Kwon BS, Weissman SM | title = cDNA sequences of two inducible T-cell genes | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 86 | issue = 6 | pages = 1963–7 | year = 1989 | pmid = 2784565 | pmc = 286825 | doi = 10.1073/pnas.86.6.1963 }}
* {{cite journal | vauthors = Schwarz H, Tuckwell J, Lotz M | title = A receptor induced by lymphocyte activation (ILA): a new member of the human nerve-growth-factor/tumor-necrosis-factor receptor family | journal = Gene | volume = 134 | issue = 2 | pages = 295–8 | year = 1993 | pmid = 8262389 | doi = 10.1016/0378-1119(93)90110-O }}
* {{cite journal | vauthors = Sica G, Chen L | title = Biochemical and immunological characteristics of 4-1BB (CD137) receptor and ligand and potential applications in cancer therapy | journal = Arch. Immunol. Ther. Exp. (Warsz.) | volume = 47 | issue = 5 | pages = 275–9 | year = 2000 | pmid = 10604232 | doi =  }}
* {{cite journal | vauthors = Schwarz H | title = Biological activities of reverse signal transduction through CD137 ligand | journal = J. Leukoc. Biol. | volume = 77 | issue = 3 | pages = 281–6 | year = 2005 | pmid = 15618293 | doi = 10.1189/jlb.0904558 }}
* {{cite journal | vauthors = Kwon BS, Weissman SM | title = cDNA sequences of two inducible T-cell genes | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 86 | issue = 6 | pages = 1963–7 | year = 1989 | pmid = 2784565 | pmc = 286825 | doi = 10.1073/pnas.86.6.1963 }}
* {{cite journal | vauthors = Zhou Z, Kim S, Hurtado J, Lee ZH, Kim KK, Pollok KE, Kwon BS | title = Characterization of human homologue of 4-1BB and its ligand | journal = Immunol. Lett. | volume = 45 | issue = 1–2 | pages = 67–73 | year = 1995 | pmid = 7622190 | doi = 10.1016/0165-2478(94)00227-I }}
* {{cite journal | vauthors = Alderson MR, Smith CA, Tough TW, Davis-Smith T, Armitage RJ, Falk B, Roux E, Baker E, Sutherland GR, Din WS | title = Molecular and biological characterization of human 4-1BB and its ligand | journal = Eur. J. Immunol. | volume = 24 | issue = 9 | pages = 2219–27 | year = 1994 | pmid = 8088337 | doi = 10.1002/eji.1830240943 }}
* {{cite journal | vauthors = Schwarz H, Tuckwell J, Lotz M | title = A receptor induced by lymphocyte activation (ILA): a new member of the human nerve-growth-factor/tumor-necrosis-factor receptor family | journal = Gene | volume = 134 | issue = 2 | pages = 295–8 | year = 1994 | pmid = 8262389 | doi = 10.1016/0378-1119(93)90110-O }}
* {{cite journal | vauthors = Schwarz H, Blanco FJ, von Kempis J, Valbracht J, Lotz M | title = ILA, a member of the human nerve growth factor/tumor necrosis factor receptor family, regulates T-lymphocyte proliferation and survival | journal = Blood | volume = 87 | issue = 7 | pages = 2839–45 | year = 1996 | pmid = 8639902 | doi =  }}
* {{cite journal | vauthors = Loo DT, Chalupny NJ, Bajorath J, Shuford WW, Mittler RS, Aruffo A | title = Analysis of 4-1BBL and laminin binding to murine 4-1BB, a member of the tumor necrosis factor receptor superfamily, and comparison with human 4-1BB | journal = J. Biol. Chem. | volume = 272 | issue = 10 | pages = 6448–56 | year = 1997 | pmid = 9045669 | doi = 10.1074/jbc.272.10.6448 }}
* {{cite journal | vauthors = Schwarz H, Arden K, Lotz M | title = CD137, a member of the tumor necrosis factor receptor family, is located on chromosome 1p36, in a cluster of related genes, and colocalizes with several malignancies | journal = Biochem. Biophys. Res. Commun. | volume = 235 | issue = 3 | pages = 699–703 | year = 1997 | pmid = 9207223 | doi = 10.1006/bbrc.1997.6870 }}
* {{cite journal | vauthors = Arch RH, Thompson CB | title = 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 | journal = Mol. Cell. Biol. | volume = 18 | issue = 1 | pages = 558–65 | year = 1998 | pmid = 9418902 | pmc = 121523 | doi =  }}
* {{cite journal | vauthors = Jang IK, Lee ZH, Kim YJ, Kim SH, Kwon BS | title = Human 4-1BB (CD137) signals are mediated by TRAF2 and activate nuclear factor-kappa B | journal = Biochem. Biophys. Res. Commun. | volume = 242 | issue = 3 | pages = 613–20 | year = 1998 | pmid = 9464265 | doi = 10.1006/bbrc.1997.8016 }}
* {{cite journal | vauthors = Kim YJ, Kim SH, Mantel P, Kwon BS | title = Human 4-1BB regulates CD28 co-stimulation to promote Th1 cell responses | journal = Eur. J. Immunol. | volume = 28 | issue = 3 | pages = 881–90 | year = 1998 | pmid = 9541583 | doi = 10.1002/(SICI)1521-4141(199803)28:03<881::AID-IMMU881>3.0.CO;2-0 }}
* {{cite journal | vauthors = Saoulli K, Lee SY, Cannons JL, Yeh WC, Santana A, Goldstein MD, Bangia N, DeBenedette MA, Mak TW, Choi Y, Watts TH | title = CD28-independent, TRAF2-dependent costimulation of resting T cells by 4-1BB ligand | journal = J. Exp. Med. | volume = 187 | issue = 11 | pages = 1849–62 | year = 1998 | pmid = 9607925 | pmc = 2212301 | doi = 10.1084/jem.187.11.1849 }}
* {{cite journal | vauthors = Langstein J, Michel J, Schwarz H | title = CD137 induces proliferation and endomitosis in monocytes | journal = Blood | volume = 94 | issue = 9 | pages = 3161–8 | year = 1999 | pmid = 10556203 | doi =  }}
* {{cite journal | vauthors = Jang LK, Lee ZH, Kim HH, Hill JM, Kim JD, Kwon BS | title = A novel leucine-rich repeat protein (LRR-1): potential involvement in 4-1BB-mediated signal transduction | journal = Mol. Cells | volume = 12 | issue = 3 | pages = 304–12 | year = 2002 | pmid = 11804328 | doi =  }}
* {{cite journal | vauthors = Cooper D, Bansal-Pakala P, Croft M | title = 4-1BB (CD137) controls the clonal expansion and survival of CD8 T cells in vivo but does not contribute to the development of cytotoxicity | journal = Eur. J. Immunol. | volume = 32 | issue = 2 | pages = 521–9 | year = 2002 | pmid = 11828369 | doi = 10.1002/1521-4141(200202)32:2<521::AID-IMMU521>3.0.CO;2-X }}
* {{cite journal | vauthors = Wilcox RA, Chapoval AI, Gorski KS, Otsuji M, Shin T, Flies DB, Tamada K, Mittler RS, Tsuchiya H, Pardoll DM, Chen L | title = Cutting edge: Expression of functional CD137 receptor by dendritic cells | journal = J. Immunol. | volume = 168 | issue = 9 | pages = 4262–7 | year = 2002 | pmid = 11970964 | doi = 10.4049/jimmunol.168.9.4262 }}
* {{cite journal | vauthors = Shulzhenko N, Morgun A, Chinellato AP, Rampim GF, Diniz RV, Almeida DR, Gerbase-DeLima M | title = CD27 but not CD70 and 4-1BB intragraft gene expression is a risk factor for acute cardiac allograft rejection in humans | journal = Transplant. Proc. | volume = 34 | issue = 2 | pages = 474–5 | year = 2002 | pmid = 12009595 | doi = 10.1016/S0041-1345(02)02600-3 }}
* {{cite journal | vauthors = Pauly S, Broll K, Wittmann M, Giegerich G, Schwarz H | title = CD137 is expressed by follicular dendritic cells and costimulates B lymphocyte activation in germinal centers | journal = J. Leukoc. Biol. | volume = 72 | issue = 1 | pages = 35–42 | year = 2002 | pmid = 12101260 | doi =  }}
{{refend}}

{{Clusters of differentiation }}
{{Tumor necrosis factor receptor superfamily}}
{{Cytokine receptor modulators}}

{{DEFAULTSORT:Cd137}}

[[Category:Oncology]]
[[Category:Immunology]]