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.
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]
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.
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[update] 5 clinical trials are active.[11]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^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. PMID18760281.
^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. PMID9464265.
Schwarz H, Tuckwell J, Lotz M (December 1993). "A receptor induced by lymphocyte activation (ILA): a new member of the human nerve-growth-factor/tumor-necrosis-factor receptor family". Gene. 134 (2): 295–8. doi:10.1016/0378-1119(93)90110-O. PMID8262389.
Sica G, Chen L (2000). "Biochemical and immunological characteristics of 4-1BB (CD137) receptor and ligand and potential applications in cancer therapy". Archivum Immunologiae et Therapiae Experimentalis. 47 (5): 275–9. PMID10604232.
Zhou Z, Kim S, Hurtado J, Lee ZH, Kim KK, Pollok KE, Kwon BS (February 1995). "Characterization of human homologue of 4-1BB and its ligand". Immunology Letters. 45 (1–2): 67–73. doi:10.1016/0165-2478(94)00227-I. PMID7622190.
Alderson MR, Smith CA, Tough TW, Davis-Smith T, Armitage RJ, Falk B, et al. (September 1994). "Molecular and biological characterization of human 4-1BB and its ligand". European Journal of Immunology. 24 (9): 2219–27. doi:10.1002/eji.1830240943. PMID8088337. S2CID35822854.
Schwarz H, Tuckwell J, Lotz M (December 1993). "A receptor induced by lymphocyte activation (ILA): a new member of the human nerve-growth-factor/tumor-necrosis-factor receptor family". Gene. 134 (2): 295–8. doi:10.1016/0378-1119(93)90110-O. PMID8262389.
Schwarz H, Arden K, Lotz M (June 1997). "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". Biochemical and Biophysical Research Communications. 235 (3): 699–703. doi:10.1006/bbrc.1997.6870. PMID9207223.
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. PMID9464265.
Langstein J, Michel J, Schwarz H (November 1999). "CD137 induces proliferation and endomitosis in monocytes". Blood. 94 (9): 3161–8. doi:10.1182/blood.V94.9.3161. PMID10556203.
Jang LK, Lee ZH, Kim HH, Hill JM, Kim JD, Kwon BS (December 2001). "A novel leucine-rich repeat protein (LRR-1): potential involvement in 4-1BB-mediated signal transduction". Molecules and Cells. 12 (3): 304–12. PMID11804328.
Shulzhenko N, Morgun A, Chinellato AP, Rampim GF, Diniz RV, Almeida DR, Gerbase-DeLima M (March 2002). "CD27 but not CD70 and 4-1BB intragraft gene expression is a risk factor for acute cardiac allograft rejection in humans". Transplantation Proceedings. 34 (2): 474–5. doi:10.1016/S0041-1345(02)02600-3. PMID12009595.
Pauly S, Broll K, Wittmann M, Giegerich G, Schwarz H (July 2002). "CD137 is expressed by follicular dendritic cells and costimulates B lymphocyte activation in germinal centers". Journal of Leukocyte Biology. 72 (1): 35–42. PMID12101260.