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Gene Review

TNFSF9  -  tumor necrosis factor (ligand) superfamily...

Homo sapiens

Synonyms: 4-1BB ligand, 4-1BB-L, 4-1BBL, CD137L, Tumor necrosis factor ligand superfamily member 9
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Disease relevance of TNFSF9


High impact information on TNFSF9


Biological context of TNFSF9


Anatomical context of TNFSF9


Associations of TNFSF9 with chemical compounds


Physical interactions of TNFSF9

  • Recent studies highlight the participation of 4-1BB and its ligand 4-1BBL in a more complex network of immune cell responses and suggest that intervening in the 4-1BB costimulatory pathway might have some potential as a therapeutic approach to immune disorders [17].

Regulatory relationships of TNFSF9


Other interactions of TNFSF9

  • Taken together, our data suggest that 4-1BB/4-1BBL interactions contribute to the persistence of gut inflammation in CD [2].
  • More recently, evidence is accumulating that 4-1BBL is more than "just" the ligand for a costimulatory molecule [18].
  • We investigated whether 4-1BB ligand (4-1BBL), a member of the tumor necrosis factor (TNF) family, is involved in the maturation process to mature myeloid DCs during in vitro DC differentiation from immature DCs derived from human umbilical cord blood (CB) CD34(+) progenitor cells [15].
  • However, in all circumstances, the induced 4-1BBL levels were low in comparison with CD80 co-stimulatory molecule [10].
  • In this study, the expression of 4-1BBL and soluble 4-1BBL (s4-1BBL) protein levels were analysed in peripheral blood of MS patients [19].

Analytical, diagnostic and therapeutic context of TNFSF9

  • The present study also implicates that modulating 4-1BB/4-1BBL costimulatory pathway may be an effective immunotherapy strategy to augment the host response [20].
  • These results indicate that blockade of 4-1BB/4-1BB ligand interactions by Ad4-1BBIg inhibited alloreactive T-cell activation and attenuated T-cell infiltration into the graft, resulting in significant prolongation of murine cardiac allograft survival [21].
  • Crystallization and preliminary X-ray crystallographic study of the extracellular domain of the 4-1BB ligand, a member of the TNF family [22].
  • Taken together, these data suggest that 4-1BBL and B7.1 have additive or synergistic effects on HIV-specific CD8 T cell responses and represent a promising combination for therapeutic vaccination for HIV [23].
  • This study indicates the complicated contribution of 4-1BBL, CD80 and CD86 on tumour and host cells in anti-tumour immune responses and a possible therapeutic application of 4-1BBL for human tumour vaccination and gene therapy [24].


  1. A novel adenovirus expressing human 4-1BB ligand enhances antitumor immunity. Yoshida, H., Katayose, Y., Unno, M., Suzuki, M., Kodama, H., Takemura, S., Asano, R., Hayashi, H., Yamamoto, K., Matsuno, S., Kudo, T. Cancer Immunol. Immunother. (2003) [Pubmed]
  2. Functional expression of 4-1BB (CD137) in the inflammatory tissue in Crohn's disease. Maerten, P., Geboes, K., De Hertogh, G., Shen, C., Cadot, P., Bullens, D.M., Van Assche, G., Penninckx, F., Rutgeerts, P., Ceuppens, J.L. Clin. Immunol. (2004) [Pubmed]
  3. Expression of costimulatory molecules (4-1BBL and Fas) and major histocompatibility class I chain-related A (MICA) in aortic tissue with Takayasu's arteritis. Seko, Y., Sugishita, K., Sato, O., Takagi, A., Tada, Y., Matsuo, H., Yagita, H., Okumura, K., Nagai, R. J. Vasc. Res. (2004) [Pubmed]
  4. Role of 4-1BB (CD137) in the functional activation of cord blood CD28(-)CD8(+) T cells. Kim, Y.J., Brutkiewicz, R.R., Broxmeyer, H.E. Blood (2002) [Pubmed]
  5. Soluble CD137 (4-1BB) ligand is released following leukocyte activation and is found in sera of patients with hematological malignancies. Salih, H.R., Schmetzer, H.M., Burke, C., Starling, G.C., Dunn, R., Pelka-Fleischer, R., Nuessler, V., Kiener, P.A. J. Immunol. (2001) [Pubmed]
  6. Defective DNA mismatch repair determines a characteristic transcriptional profile in proximal colon cancers. di Pietro, M., Bellver, J.S., Menigatti, M., Bannwart, F., Schnider, A., Russell, A., Truninger, K., Jiricny, J., Marra, G. Gastroenterology (2005) [Pubmed]
  7. OX40 ligand shuts down IL-10-producing regulatory T cells. Ito, T., Wang, Y.H., Duramad, O., Hanabuchi, S., Perng, O.A., Gilliet, M., Qin, F.X., Liu, Y.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  8. Costimulatory ligand 4-1BBL (CD137L) as an efficient adjuvant for human antiviral cytotoxic T cell responses. Bukczynski, J., Wen, T., Ellefsen, K., Gauldie, J., Watts, T.H. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  9. Constitutive expression of functional 4-1BB (CD137) ligand on carcinoma cells. Salih, H.R., Kosowski, S.G., Haluska, V.F., Starling, G.C., Loo, D.T., Lee, F., Aruffo, A.A., Trail, P.A., Kiener, P.A. J. Immunol. (2000) [Pubmed]
  10. Lipopolysaccharide preferentially induces 4-1BB ligand expression on human monocyte-derived dendritic cells. Lee, P.K., Chang, C.J., Lin, C.M. Immunol. Lett. (2003) [Pubmed]
  11. Death-inducing tumour necrosis factor (TNF) superfamily ligands and receptors are transcribed in human placentae, cytotrophoblasts, placental macrophages and placental cell lines. Phillips, T.A., Ni, J., Hunt, J.S. Placenta (2001) [Pubmed]
  12. Immunotherapy targeting 4-1BB and its ligand. Vinay, D.S., Kwon, B.S. Int. J. Hematol. (2006) [Pubmed]
  13. Production of recombinant human trimeric CD137L (4-1BBL). Cross-linking is essential to its T cell co-stimulation activity. Rabu, C., Quéméner, A., Jacques, Y., Echasserieau, K., Vusio, P., Lang, F. J. Biol. Chem. (2005) [Pubmed]
  14. 4-1BB-ligand is regulated on human dendritic cells and induces the production of IL-12. Laderach, D., Wesa, A., Galy, A. Cell. Immunol. (2003) [Pubmed]
  15. 4-1BB ligand stimulation enhances myeloid dendritic cell maturation from human umbilical cord blood CD34+ progenitor cells. Kim, Y.J., Li, G., Broxmeyer, H.E. J. Hematother. Stem Cell Res. (2002) [Pubmed]
  16. Cloning, structural organization and chromosomal mapping of rat costimulatory molecule 4-1BBL. Dong, Q.M., Ma, L.J., Zhang, G.B., Wu, Y.F., Shen, J.Y., Chen, Y., Chen, Y.J., Pu, X.K., Hang, S.Y., Zhang, X.G. Acta Biochim. Biophys. Sin. (Shanghai) (2005) [Pubmed]
  17. New insights into the role of 4-1BB in immune responses: beyond CD8+ T cells. Kwon, B., Lee, H.W., Kwon, B.S. Trends Immunol. (2002) [Pubmed]
  18. 4-1 BB ligand--just another costimulating molecule? Salih, H.R., Kiener, P.A., Nüssler, V. International journal of clinical pharmacology and therapeutics. (2002) [Pubmed]
  19. Increased Soluble 4-1BB Ligand (4-1BBL) Levels in Peripheral Blood of Patients with Multiple Sclerosis. Liu, G.Z., Gomes, A.C., Putheti, P., Karrenbauer, V., Kostulas, K., Press, R., Hillert, J., Hjelmström, P., Gao, X.G. Scand. J. Immunol. (2006) [Pubmed]
  20. Expression of co-stimulator 4-1BB molecule in hepatocellular carcinoma and adjacent non-tumor liver tissue, and its possible role in tumor immunity. Wan, Y.L., Zheng, S.S., Zhao, Z.C., Li, M.W., Jia, C.K., Zhang, H. World J. Gastroenterol. (2004) [Pubmed]
  21. Gene therapy using adenoviral vector encoding 4-1BBIg gene significantly prolonged murine cardiac allograft survival. Huang, B.J., Yin, H., Huang, Y.F., Xu, J.F., Xiong, P., Feng, W., Zheng, F., Xu, Y., Fang, M., Gong, F.L. Transpl. Immunol. (2006) [Pubmed]
  22. Crystallization and preliminary X-ray crystallographic study of the extracellular domain of the 4-1BB ligand, a member of the TNF family. Byun, J.S., Kim, D.U., Ahn, B., Kwon, B.S., Cho, H.S. Acta Crystallograph. Sect. F Struct. Biol. Cryst. Commun. (2006) [Pubmed]
  23. Enhancement of HIV-specific CD8 T cell responses by dual costimulation with CD80 and CD137L. Bukczynski, J., Wen, T., Wang, C., Christie, N., Routy, J.P., Boulassel, M.R., Kovacs, C.M., Macdonald, K.S., Ostrowski, M., Sekaly, R.P., Bernard, N.F., Watts, T.H. J. Immunol. (2005) [Pubmed]
  24. Tumour rejection by gene transfer of 4-1BB ligand into a CD80(+) murine squamous cell carcinoma and the requirements of co-stimulatory molecules on tumour and host cells. Mogi, S., Sakurai, J., Kohsaka, T., Enomoto, S., Yagita, H., Okumura, K., Azuma, M. Immunology (2000) [Pubmed]
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