Property Summary

NCBI Gene PubMed Count 63
PubMed Score 177.62
PubTator Score 101.30

Knowledge Summary


No data available


  Disease (3)


  Differential Expression (7)

Disease log2 FC p
malignant mesothelioma 3.600 3.2e-09
astrocytic glioma -1.200 3.9e-02
ependymoma -1.400 4.3e-02
oligodendroglioma -1.200 4.6e-02
medulloblastoma, large-cell -1.100 1.4e-04
lung cancer -1.900 6.7e-05
active ulcerative colitis 2.467 4.1e-02

Gene RIF (52)

26872462 blocking of both OX-40L and 4-1BBL reversed radiation-enhanced T-cell killing of human tumor targets as well as T-cell survival and activation.
26125931 In vitro immunotherapy is described for anti-prostate cancer effects of cytotoxic T lymphocytes induction by recombinant adenovirus mediated PSMA/4-1BBL dendritic cells.
26116899 HIV-1 Vpr upregulates the gene expression of TNFSF9 in human monocyte-derived dendritic cells
25872647 vaccination with recombinant attenuated Salmonella harboring the CEACAM6 and 4-1BBL gene efficiently increased the number of CD3+CD8+ TIL and NK cells, decreased the number of FOXP3 cells and inhibited the development of DMH-induced colorectal cancer
25631633 CD137L is overexpressed in non-small cell lung cancer specimens and positive expression of CD137L was associated with better overall survival.
24899613 Elevated plasma levels and monocyte-associated expression of CD137 ligand in patients with acute atherothrombotic stroke
24639347 monocytes interact with iNKT cells to increase expression of 4-1BBL and 4-1BB, and in conjunction with this pathway, maintain their numbers at baseline.
24198185 Hence, the targeted combination of IL-15 and 4-BBL in the form of a trifunctional antibody-fusion protein is a promising new approach for cancer immunotherapy.
24084649 TIRAP and IRAK2 are critical for the sustained inflammatory response that is mediated by late-phase signaling by the TLR-4-1BBL complex.
23620528 Data show that TNFR1 associates with CD137L and is required for CD137L reverse signaling.
23095505 CD137L is a novel diagnostic marker of subtypes of non-Hodgkin B-cell lymphomas.
22797667 this is the first study to indicate that this member of the TNF superfamily, CD137, is modulated by SAHA treatment in breast
22526397 signaling through CD137L in non-hematopoietic cells such as epithelial cells and endothelial cells has been shown to play an essential role in sterile inflammation by regulating immune cell recruitment. [Review]
22021067 Stimulation of non-adherent PBMC with OVCAR-3 cells expressing 4-1BB ligand (4-1BBL) or IL-12 resulted in preferential expansion of the NK cell population.
21745658 Data indicate that ex4-1BBL augments 4-1BB expression not only on the primed T cell, but also on DC.
21153322 4-1BBL and TRAF1 in the CD8 T cell response to influenza virus and HIV
20670353 K562-MICA-4-1BBL-IL-15 cells would be developed for expansion of NK cells ex vivo and may have important implications for clinical immunotherapy.
20628624 Meta-analysis of gene-disease association. (HuGE Navigator)
20568250 Observational study of gene-disease association. (HuGE Navigator)
20520765 These data point to a hitherto unrecognized role of CD137 and CD137 ligand in multiple myeloma cell biology.
20438785 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
20422976 The expression of CD137L might play an important role in the development of laryngeal carcinomas.
20406964 Observational study of gene-disease association. (HuGE Navigator)
20303781 TNFSF9 mRNA levels in peripheral blood mononuclear cells may be associated with primary biliary cirrhosis progression.
20237496 Observational study of gene-disease association. (HuGE Navigator)
20032458 the structure of the trimer of human 4-1BB ligand is unique among members of the tumor necrosis factor superfamily
20008791 Cocultures of Natural killer (NK) cells with CD137L transfectants confirmed that human CD137 inhibits NK-cell reactivity, while activating signals were transduced by its counterpart on NK cells in mice.
19773279 Observational study of gene-disease association. (HuGE Navigator)
19759901 4-1BBL and 4-1BB may have immunomodulatory functions, as shown by the anti-leukemia activity of MS-275 histone deacetylase inhibitor
19684160 reverse signaling of 4-1BBL promotes the differentiation of potent T(h)1-inducing dendritic cells from human monocytes.
19573080 Observational study of gene-disease association. (HuGE Navigator)
19423540 Observational study of gene-disease association. (HuGE Navigator)
19225975 (c)4-1BBL can be expressed on mononuclear blood cells in acute myeloid leukemia, myelodysplasia or non-Hodgkin lymphoma and can be coexpressed on lymphoid or myeloid malignant cells and on dendritic cells differentiated from AML-blasts.
19217084 in cells costimulated with CD80/86 that had downregulated CD28 expression and ceased to proliferate, reactivation of proliferation by 4-1BBL costimulation also restored their CD28 expression
19029446 PGE(2) induced the expression of the costimulatory molecules OX40L, CD70, and 4-1BBL on human dendritic cells.
18395851 deliver new insights into the multiple effects of reverse signaling of CD137L in human DC during the initiation of an adaptive immune response
18026115 CD80 and 4-1BBL induce auto- and transcostimulation in tumor cells
17977894 T cells that had become non-responsive to anti-CD3 could be reactivated to proliferate when costimulated with 4-1BBL, either alone or combined with CD80/CD86.
17972956 selective immunosuppression through MSCs may perhaps occur partly through an increase in CD137L+ on T-lymphocytes
17855813 Reverse signalling by CD137 ligand is mediated by protein tyrosine kinases, p38 mitogen activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK)1,2, MAP/ERK kinase (MEK), Phosphoinositide-3-kinase (PI3-K) and protein kinase A (PKA).
17496895 Here we document a function for the TNF family member 4-1BB ligand (4-1BBL) in sustaining TLR-induced TNF production
16970683 Elevated plasma levels of 4-1BBL in multiple sclerosis patients may function as a self-regulatory mechanism of the 4-1BB/4-1BBL pathway involved in the disease process.
16596186 Significantly lower CD137 ligand is associated with colorectal cancer patients
16287062 Signaling through 4-1BB-L allows B cells to proliferate and the expression of its ligand, by the intra-tumoral mesh of follicular dendritic cells (FDC), could thus serve as a paracrine loop facilitating growth and survival of MCL cells
16204238 trimeric CD137L (4-1BBL) requires cross-linking for its T cell co-stimulation activity
15031666 Data suggest that levels of soluble 4-1BB and 4-1BB ligand in sera at the time of diagnosis may be indicative of the severity and outcome of rheumatoid arthritis.
14752253 4-1BB/4-1BBL and Fas/FasL pathways play important roles in vascular injury in Takayasu's arteritis.
14746806 Data show that reverse signaling via 4-1BB-ligand enhanced interleukin-12beta mRNA and the secretion of IL-12 p70 in various antigen-presenting cells, including monocytes.
13130507 First evidence of expression and synthesis of CD137 and its ligand by human brain cells.
12645943 4-1 BB ligand can costimulate human CD28- T cells, resulting in cell division, inflammatory cytokine production, increased perforin levels, enhancement of cytolytic effector function, as well as the up-regulation of the anti-apoptotic protein Bcl-X(L).
12590704 Stimulation of 4-1BBL on DCs with 4-1BB-Fc or with 4-1BB-transfected Jurkat cells resulted in acquisition of capacity for the immature DCs to produce IL-12, suggesting that 4-1BBL may be an important mediator for maturation of CD11c(+) myeloid DCs
11994439 4-1BBL provides a costimulatory signal for T cell activation, thereby allowing T cell expansion as well as cytokine production and the development of cytolytic effector function.

AA Sequence


Text Mined References (63)

PMID Year Title
26872462 2016 Effector function of CTLs is increased by irradiated colorectal tumor cells that modulate OX-40L and 4-1BBL and is reversed following dual blockade.
26646413 2016 Comparative genomic analysis of eutherian tumor necrosis factor ligand genes.
26125931 2015 Anti-prostate cancer effects of CTL cell induction in vitro by recombinant adenovirus mediated PSMA/4-1BBL dendritic cells: an immunotherapy study.
25872647 2015 Recombinant Salmonella-based CEACAM6 and 4-1BBL vaccine enhances T-cell immunity and inhibits the development of colorectal cancer in rats: In vivo effects of vaccine containing 4-1BBL and CEACAM6.
25631633 2015 CD137 ligand-mediated reverse signaling inhibits proliferation and induces apoptosis in non-small cell lung cancer.
24899613 2014 Elevated plasma levels and monocyte-associated expression of CD137 ligand in patients with acute atherothrombotic stroke.
24639347 2014 Involvement of the 4-1BB/4-1BBL pathway in control of monocyte numbers by invariant NKT cells.
24198185 2014 Combining antibody-directed presentation of IL-15 and 4-1BBL in a trifunctional fusion protein for cancer immunotherapy.
24084649 2013 The TNF family member 4-1BBL sustains inflammation by interacting with TLR signaling components during late-phase activation.
23620528 2013 Tumor necrosis factor receptor 1 associates with CD137 ligand and mediates its reverse signaling.
23095505 2013 CD137 ligand is expressed in primary and secondary lymphoid follicles and in B-cell lymphomas: diagnostic and therapeutic implications.
22797667 2012 SAHA/Vorinostat induces the expression of the CD137 receptor/ligand system and enhances apoptosis mediated by soluble CD137 receptor in a human breast cancer cell line.
22526397 2012 Reverse signaling through the co-stimulatory ligand, CD137L, as a critical mediator of sterile inflammation.
22021067 2012 Long-term proliferation of functional human NK cells, with conversion of CD56(dim) NK cells to a CD56 (bright) phenotype, induced by carcinoma cells co-expressing 4-1BBL and IL-12.
21745658 2011 Extracellular domain of human 4-1BBL enhanced the function of cytotoxic T-lymphocyte induced by dendritic cell.
21153322 2011 Role of 4-1BBL and TRAF1 in the CD8 T cell response to influenza virus and HIV.
20670353 2010 Ex vivo expansion of natural killer cells with high cytotoxicity by K562 cells modified to co-express major histocompatibility complex class I chain-related protein A, 4-1BB ligand, and interleukin-15.
20628624 2010 Evaluation of candidate stromal epithelial cross-talk genes identifies association between risk of serous ovarian cancer and TERT, a cancer susceptibility "hot-spot".
20568250 2010 Common single nucleotide polymorphisms in immunoregulatory genes and multiple myeloma risk among women in Connecticut.
20520765 2010 Inhibition of proliferation and induction of apoptosis in multiple myeloma cell lines by CD137 ligand signaling.
20438785 2010 Polymorphisms in innate immunity genes and risk of childhood leukemia.
20422976 2010 [Clinicopathological significance of CD137L expression in laryngeal carcinoma].
20406964 2010 Risk of meningioma and common variation in genes related to innate immunity.
20303781 2010 TNFSF9 expression in primary biliary cirrhosis and its clinical significance.
20237496 2010 New genetic associations detected in a host response study to hepatitis B vaccine.
20032458 2010 The structure of the trimer of human 4-1BB ligand is unique among members of the tumor necrosis factor superfamily.
20008791 2010 CD137 ligand mediates opposite effects in human and mouse NK cells and impairs NK-cell reactivity against human acute myeloid leukemia cells.
19773279 2009 Association between genetic variants in VEGF, ERCC3 and occupational benzene haematotoxicity.
19759901 2009 Anti-leukemia activity of MS-275 histone deacetylase inhibitor implicates 4-1BBL/4-1BB immunomodulatory functions.
19684160 2009 A novel approach to induce human DCs from monocytes by triggering 4-1BBL reverse signaling.
19573080 2009 Common genetic variants in candidate genes and risk of familial lymphoid malignancies.
19423540 2009 Common variation in genes related to innate immunity and risk of adult glioma.
19225975 2009 The role of soluble and cell-surface expressed 4-1BB ligand in patients with malignant hemopoietic disorders.
19217084 2009 4-1BBL costimulation retrieves CD28 expression in activated T cells.
19029446 2009 Prostaglandin E(2) enhances T-cell proliferation by inducing the costimulatory molecules OX40L, CD70, and 4-1BBL on dendritic cells.
18395851 2008 CD137 ligand reverse signaling has multiple functions in human dendritic cells during an adaptive immune response.
18026115 2007 T cell-encoded CD80 and 4-1BBL induce auto- and transcostimulation, resulting in potent tumor rejection.
17977894 2007 Co-stimulation with 4-1BB ligand allows extended T-cell proliferation, synergizes with CD80/CD86 and can reactivate anergic T cells.
17972956 2008 Marked improvement of severe progressive systemic sclerosis after transplantation of mesenchymal stem cells from an allogeneic haploidentical-related donor mediated by ligation of CD137L.
17855813 2007 Signal transduction mechanisms of CD137 ligand in human monocytes.
17496895 2007 Cell surface 4-1BBL mediates sequential signaling pathways 'downstream' of TLR and is required for sustained TNF production in macrophages.
16970683 2006 Increased soluble 4-1BB ligand (4-1BBL) levels in peripheral blood of patients with multiple sclerosis.
16596186 2006 Expression of CD137 and CD137 ligand in colorectal cancer patients.
16341674 2005 Transcriptome analysis of human gastric cancer.
16287062 2006 Mantle cell lymphomas acquire increased expression of CCL4, CCL5 and 4-1BB-L implicated in cell survival.
16204238 2005 Production of recombinant human trimeric CD137L (4-1BBL). Cross-linking is essential to its T cell co-stimulation activity.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15031666 2004 Serum concentrations of soluble 4-1BB and 4-1BB ligand correlated with the disease severity in rheumatoid arthritis.
14752253 Expression of costimulatory molecules (4-1BBL and Fas) and major histocompatibility class I chain-related A (MICA) in aortic tissue with Takayasu's arteritis.
14746806 2003 4-1BB-ligand is regulated on human dendritic cells and induces the production of IL-12.
13130507 2003 Expression of CD137 and its ligand in human neurons, astrocytes, and microglia: modulation by FGF-2.
12645943 2003 Costimulation of human CD28- T cells by 4-1BB ligand.
12590704 2002 4-1BB ligand stimulation enhances myeloid dendritic cell maturation from human umbilical cord blood CD34+ progenitor cells.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11564827 2001 Soluble CD137 (4-1BB) ligand is released following leukocyte activation and is found in sera of patients with hematological malignancies.
10946324 2000 Constitutive expression of functional 4-1BB (CD137) ligand on carcinoma cells.
10850651 2000 4-1BB: still in the midst of darkness.
10528187 1999 4-1BB ligand, a member of the TNF family, is important for the generation of antiviral CD8 T cell responses.
9607925 1998 CD28-independent, TRAF2-dependent costimulation of resting T cells by 4-1BB ligand.
9418902 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.
9045669 1997 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.
8405064 1993 Molecular cloning of a ligand for the inducible T cell gene 4-1BB: a member of an emerging family of cytokines with homology to tumor necrosis factor.
8088337 1994 Molecular and biological characterization of human 4-1BB and its ligand.