Clipboard, Search History, and several other advanced features are temporarily unavailable. 1 Department of Internal Medicine II, University Hospital of the Eberhard Karls University, Tübingen, Gernany. Helmut.Salih@med.uni-tuebingen.de 1 Department of Internal Medicine II, University Hospital of the Eberhard Karls University, Tübingen, Gernany. Helmut.Salih@med.uni-tuebingen.de Initially, scientific interest in the 4-1BB/4-1BB Ligand system focused on the role of the 4-1BB (CD137) receptor in the costimulation of T cells. More recently, evidence is accumulating that 4-1BBL is more than \"just\" the ligand for a costimulatory molecule. In this review we discuss the functional properties of 4-1BB Ligand such as its preference for CD8 positive T cells and the differences to costimulation via the B7/CD28 system. Furthermore, the available data regarding its ability to transduce signals bidirectionally, i.e. also back into the ligand bearing cell, its release as a soluble form following shedding from the cell surface, and its role in the interaction of tumor cells with the immune system are reviewed. Cheuk AT, et al. Cancer Gene Ther. 2004 Mar;11(3):215-26. doi: 10.1038/sj.cgt.7700670. Cancer Gene Ther. 2004. PMID: 14671675 Wen T, et al. J Immunol. 2002 May 15;168(10):4897-906. doi: 10.4049/jimmunol.168.10.4897. J Immunol. 2002. PMID: 11994439 Semin Immunol. 1998 Dec;10(6):481-9. doi: 10.1006/smim.1998.0157. Semin Immunol. 1998. PMID: 9826581 Eckstrum K, et al. Cell Tissue Res. 2011 Jun;344(3):567-76. doi: 10.1007/s00441-011-1171-0. Epub 2011 May 12. Cell Tissue Res. 2011. PMID: 21560035 Free PMC article.