4 1BB


Gene Symbol: 4 1BB
Description: TNF receptor superfamily member 9
Alias: 4-1BB, CD137, CDw137, ILA, tumor necrosis factor receptor superfamily member 9, 4-1BB ligand receptor, CD137 antigen, T cell antigen ILA, T-cell antigen 4-1BB homolog, homolog of mouse 4-1BB, induced by lymphocyte activation (ILA), interleukin-activated receptor, homolog of mouse Ly63, receptor protein 4-1BB
Species: human
Products:     4 1BB

Top Publications

  1. Schwarz H. Biological activities of reverse signal transduction through CD137 ligand. J Leukoc Biol. 2005;77:281-6 pubmed
    b>CD137 is a member of the tumor necrosis factor receptor family and a potent regulator of T cell activities...
  2. Kwon B, Weissman S. cDNA sequences of two inducible T-cell genes. Proc Natl Acad Sci U S A. 1989;86:1963-7 pubmed
    ..Both peptides contain putative leader sequences. The protein encoded by 4-1BB also has a potential membrane anchor segment and other features also seen in known receptor proteins. ..
  3. Arch R, Thompson C. 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. Mol Cell Biol. 1998;18:558-65 pubmed
    ..Taken together, our results indicate that 4-1BB and Ox40 bind TRAF proteins to initiate a signaling cascade leading to activation of nuclear factor kappaB. ..
  4. Jang I, Lee Z, Kim Y, Kim S, Kwon B. Human 4-1BB (CD137) signals are mediated by TRAF2 and activate nuclear factor-kappa B. Biochem Biophys Res Commun. 1998;242:613-20 pubmed
    Human 4-1BB (CD137), a member of the tumor necrosis factor receptor (TNFR) superfamily, costimulates T cell activation...
  5. Pauly S, Broll K, Wittmann M, Giegerich G, Schwarz H. CD137 is expressed by follicular dendritic cells and costimulates B lymphocyte activation in germinal centers. J Leukoc Biol. 2002;72:35-42 pubmed
    b>CD137, a member of the TNF receptor family, and its ligand are expressed on T lymphocytes and antigen-presenting cells (APC), respectively. During interaction with APC, T lymphocytes receive a potent, costimulatory signal through CD137...
  6. Jung H, Choi S, Choi J, Kwon B. Serum concentrations of soluble 4-1BB and 4-1BB ligand correlated with the disease severity in rheumatoid arthritis. Exp Mol Med. 2004;36:13-22 pubmed
    ..The augmented secretion of s4-1BB and s4-1BBL levels into the serum may reflect the clinical symptoms of RA and levels of s4-1BB and s4-1BBL in sera at the time of diagnosis may be indicative of the severity and outcome of RA. ..
  7. Pichler K, Kattan T, Gentzsch J, Kress A, Taylor G, Bangham C, et al. Strong induction of 4-1BB, a growth and survival promoting costimulatory receptor, in HTLV-1-infected cultured and patients' T cells by the viral Tax oncoprotein. Blood. 2008;111:4741-51 pubmed publisher
    ..Tax on costimulatory receptors in T cells with repressible Tax and found that among these receptors 4-1BB (TNFRSF9/CD137/ILA) was induced most strongly...
  8. Shao Z, Schwarz H. CD137 ligand, a member of the tumor necrosis factor family, regulates immune responses via reverse signal transduction. J Leukoc Biol. 2011;89:21-9 pubmed publisher
    b>CD137 (4-1BB, TNFR superfamily 9) and its ligand are members of the TNFR and TNF families, respectively, and are involved in the regulation of a wide range of immune activities...
  9. Fernández Do Porto D, Jurado J, Pasquinelli V, Alvarez I, Aspera R, Musella R, et al. CD137 differentially regulates innate and adaptive immunity against Mycobacterium tuberculosis. Immunol Cell Biol. 2012;90:449-56 pubmed publisher
    ..Thus, here we investigated the function of CD137 and CD137L, molecules known to have a central role in immune regulation, during human tuberculosis (TB)...

More Information

Publications116 found, 100 shown here

  1. Alderson M, Smith C, Tough T, Davis Smith T, Armitage R, Falk B, et al. Molecular and biological characterization of human 4-1BB and its ligand. Eur J Immunol. 1994;24:2219-27 pubmed
    ..In contrast, ligation of 4-1BB on T cell clones enhanced activation-induced cell death when triggered by engagement of the TCR/CD3 complex. ..
  2. Loo D, Chalupny N, Bajorath J, Shuford W, Mittler R, Aruffo A. 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. J Biol Chem. 1997;272:6448-56 pubmed
    The T cell activation antigen 4-1BB (CDw137) is a distantly related member of the tumor necrosis factor receptor family of cell surface receptors...
  3. Saoulli K, Lee S, Cannons J, Yeh W, Santana A, Goldstein M, et al. CD28-independent, TRAF2-dependent costimulation of resting T cells by 4-1BB ligand. J Exp Med. 1998;187:1849-62 pubmed
    ..Thus 4-1BB, via the TRAF2 molecule, can provide CD28-independent costimulatory signals to resting T cells. ..
  4. Wilcox R, Chapoval A, Gorski K, Otsuji M, Shin T, Flies D, et al. Cutting edge: Expression of functional CD137 receptor by dendritic cells. J Immunol. 2002;168:4262-7 pubmed
    ..We report in this work that freshly isolated mouse splenic DCs and bone marrow-derived DCs express CD137 on the cell surface and in soluble form. Triggering CD137 increased the secretion of IL-6 and IL-12 from DCs...
  5. Nagila A, Netsawang J, Srisawat C, Noisakran S, Morchang A, Yasamut U, et al. Role of CD137 signaling in dengue virus-mediated apoptosis. Biochem Biophys Res Commun. 2011;410:428-33 pubmed publisher
    ..Expression of CD137, which is a member of the tumor necrosis factor receptor family, increased significantly in HepG2 cells expressing ..
  6. Lee S, Park Y, Eun S, Madireddi S, Cheroutre H, Croft M. Cutting edge: 4-1BB controls regulatory activity in dendritic cells through promoting optimal expression of retinal dehydrogenase. J Immunol. 2012;189:2697-701 pubmed publisher
    ..How RALDH expression is regulated is unclear. We found that 4-1BB (CD137), a member of the TNFR family, together with CD103, marked mesenteric lymph node DC with the highest level of ..
  7. Anderson M, Zhao S, Freud A, Czerwinski D, Kohrt H, Alizadeh A, et al. CD137 is expressed in follicular dendritic cell tumors and in classical Hodgkin and T-cell lymphomas: diagnostic and therapeutic implications. Am J Pathol. 2012;181:795-803 pubmed publisher
    b>CD137 (also known as 4-1BB and TNFRSF9) is a member of the tumor necrosis factor receptor superfamily...
  8. Kozela E, Juknat A, Gao F, Kaushansky N, Coppola G, Vogel Z. Pathways and gene networks mediating the regulatory effects of cannabidiol, a nonpsychoactive cannabinoid, in autoimmune T cells. J Neuroinflammation. 2016;13:136 pubmed publisher
    ..These findings put forward mechanism by which CBD exerts its anti-inflammatory effects as well as explain the beneficial role of CBD in pathological memory T cells and in autoimmune diseases. ..
  9. Azpilikueta A, Agorreta J, Labiano S, Pérez Gracia J, Sánchez Paulete A, Aznar M, et al. Successful Immunotherapy against a Transplantable Mouse Squamous Lung Carcinoma with Anti-PD-1 and Anti-CD137 Monoclonal Antibodies. J Thorac Oncol. 2016;11:524-36 pubmed publisher
    ..Immunocompetent mice subcutaneously implanted with this syngeneic cell line were treated with anti-CD137 and/or anti-PD-1 mAbs and monitored for tumor growth/progression or assessed for intratumoral leukocyte ..
  10. Claycombe K, Vomhof DeKrey E, Garcia R, Johnson W, Uthus E, Roemmich J. Decreased beige adipocyte number and mitochondrial respiration coincide with increased histone methyl transferase (G9a) and reduced FGF21 gene expression in Sprague-Dawley rats fed prenatal low protein and postnatal high-fat diets. J Nutr Biochem. 2016;31:113-21 pubmed publisher
    ..Results showed that subc-AT and liver FGF21, PRDM16 and BA marker CD137 mRNA increase with postnatal HF diet in maternal NP group rats...
  11. de Wit J, Emmelot M, Poelen M, Lanfermeijer J, Han W, van Els C, et al. The Human CD4+ T Cell Response against Mumps Virus Targets a Broadly Recognized Nucleoprotein Epitope. J Virol. 2019;93: pubmed publisher
    ..Upon peptide-specific stimulation, the T cell clone expressed the activation marker CD137 and produced gamma interferon, tumor necrosis factor, and interleukin-10 in a HLA-DR4-restricted manner...
  12. Sanmamed M, Pastor F, Rodriguez A, Perez Gracia J, Rodriguez Ruiz M, Jure Kunkel M, et al. Agonists of Co-stimulation in Cancer Immunotherapy Directed Against CD137, OX40, GITR, CD27, CD28, and ICOS. Semin Oncol. 2015;42:640-55 pubmed publisher
    ..lymphocytes such as CD28 or CD27 and others whose expression is induced upon recent previous antigen priming, ie, CD137, GITR, OX40, and ICOS...
  13. Comba A, Almada L, Tolosa E, Iguchi E, Marks D, Vara Messler M, et al. Nuclear Factor of Activated T Cells-dependent Down-regulation of the Transcription Factor Glioma-associated Protein 1 (GLI1) Underlies the Growth Inhibitory Properties of Arachidonic Acid. J Biol Chem. 2016;291:1933-47 pubmed publisher
    ..Collectively, these results define a novel mechanism underlying AA antitumoral functions that may serve as a foundation for future PUFA-based therapeutic approaches. ..
  14. Ascierto P, Agarwala S, Botti G, Cesano A, Ciliberto G, Davies M, et al. Future perspectives in melanoma research : Meeting report from the "Melanoma Bridge". Napoli, December 1st-4th 2015. J Transl Med. 2016;14:313 pubmed
    ..Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors on T cells and other approaches such as adoptive cell transfer are tested for clinical efficacy in ..
  15. Pato A, Eisenberg G, Machlenkin A, Margalit A, Cafri G, Frankenburg S, et al. Messenger RNA encoding constitutively active Toll-like receptor 4 enhances effector functions of human T cells. Clin Exp Immunol. 2015;182:220-9 pubmed publisher
    ..Our results demonstrate that caTLR-4 is capable of exerting multiple T cell-enhancing effects and can potentially be used as a genetic adjuvant in adoptive cell therapy. ..
  16. Kutyrev I, Cleveland B, Leeds T, Wiens G. Proinflammatory cytokine and cytokine receptor gene expression kinetics following challenge with Flavobacterium psychrophilum in resistant and susceptible lines of rainbow trout (Oncorhynchus mykiss). Fish Shellfish Immunol. 2016;58:542-553 pubmed publisher
    ..This study furthers the understanding of the immune response following Fp challenge and differences in gene expression associated with selective breeding for disease resistance. ..
  17. Kim J, Podolanczuk A, Borker P, Kawut S, Raghu G, Kaufman J, et al. Obstructive Sleep Apnea and Subclinical Interstitial Lung Disease in the Multi-Ethnic Study of Atherosclerosis (MESA). Ann Am Thorac Soc. 2017;14:1786-1795 pubmed publisher
    ..0% HAA increment (95% confidence interval [CI], 1.4-6.8%; P?=?0.003) and 35% increased odds of ILA (95% CI, 13-61%; P?=?0.001)...
  18. Rodriguez Ruiz M, Rodriguez I, Leaman O, Lopez Campos F, Montero A, Conde A, et al. Immune mechanisms mediating abscopal effects in radioimmunotherapy. Pharmacol Ther. 2019;196:195-203 pubmed publisher
    ..Immunotherapies such as immunomodulatory monoclonal antibodies (anti-PD-1, anti-CTLA-4, anti-CD137, anti-OX40, anti-CD40, anti-TGFβ), TLR-agonists, and adoptive T-cell therapy have been synergistically combined ..
  19. Fu T, Seok S, Choi S, Huang Z, Suino Powell K, Xu H, et al. MicroRNA 34a inhibits beige and brown fat formation in obesity in part by suppressing adipocyte fibroblast growth factor 21 signaling and SIRT1 function. Mol Cell Biol. 2014;34:4130-42 pubmed publisher
    ..Remarkably, downregulation of miR-34a increased coexpression of the beige fat-specific marker CD137 and the browning marker UCP1 in all types of white fat, including visceral fat, and promoted additional browning ..
  20. Petrov P, Palou A, Bonet M, Ribot J. Cell-Autonomous Brown-Like Adipogenesis of Preadipocytes From Retinoblastoma Haploinsufficient Mice. J Cell Physiol. 2016;231:1941-52 pubmed publisher
    ..genes (Pparg, Ppargc1a, Ppargc1b, Prdm16, Cpt1b) but not of purported beige/brite transcriptional markers (Cd137, Tmem26, Tbx1, Slc27a1, Hoxc9, Shox2)...
  21. Laiglesia L, Lorente Cebrián S, Prieto Hontoria P, Fernández Galilea M, Ribeiro S, Sainz N, et al. Eicosapentaenoic acid promotes mitochondrial biogenesis and beige-like features in subcutaneous adipocytes from overweight subjects. J Nutr Biochem. 2016;37:76-82 pubmed publisher
    ..PR domain containing 16, uncoupling protein 1 and cell death-inducing DFFA-like effector A, T-Box protein 1 and CD137. Our results suggest that EPA induces a remodeling of adipocyte metabolism preventing fat storage and promoting ..
  22. Ascierto P, Atkins M, Bifulco C, Botti G, COCHRAN A, Davies M, et al. Future perspectives in melanoma research: meeting report from the "Melanoma Bridge": Napoli, December 3rd-6th 2014. J Transl Med. 2015;13:374 pubmed publisher
    ..Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors and other approaches such as adoptive cell transfer demonstrate clinical benefit in patients with ..
  23. Imran K, Rahman N, Yoon D, Jeon M, Lee B, Kim Y. Cryptotanshinone promotes commitment to the brown adipocyte lineage and mitochondrial biogenesis in C3H10T1/2 mesenchymal stem cells via AMPK and p38-MAPK signaling. Biochim Biophys Acta Mol Cell Biol Lipids. 2017;1862:1110-1120 pubmed publisher
    ..of brown-fat signature genes including Ucp1, Prdm16, Pgc-1?, Cidea, Zic1, and beige-cell-specific genes such as CD137, Hspb7, Cox2, and Tmem26...
  24. Faus I, Niñoles R, Kesari V, Llabata P, Tam E, Nebauer S, et al. Arabidopsis ILITHYIA protein is necessary for proper chloroplast biogenesis and root development independent of eIF2? phosphorylation. J Plant Physiol. 2018;224-225:173-182 pubmed publisher
    ..factor 2 (eIF2), performed in Arabidopsis by the protein kinase GCN2 which interacts and is activated by ILITHYIA(ILA). ILA is involved in plant immunity and its mutant lines present phenotypes not shared by the gcn2 mutants...
  25. Lagali N, Badian R, Liu X, Feldreich T, Arnlov J, Utheim T, et al. Dendritic cell maturation in the corneal epithelium with onset of type 2 diabetes is associated with tumor necrosis factor receptor superfamily member 9. Sci Rep. 2018;8:14248 pubmed publisher
    ..IVCM enables this process to be monitored non-invasively in the eye. ..
  26. Barrett D, Singh N, Liu X, Jiang S, June C, Grupp S, et al. Relation of clinical culture method to T-cell memory status and efficacy in xenograft models of adoptive immunotherapy. Cytotherapy. 2014;16:619-30 pubmed publisher
  27. Lakritz J, Robinson J, Polydefkis M, Miller A, Burdo T. Loss of intraepidermal nerve fiber density during SIV peripheral neuropathy is mediated by monocyte activation and elevated monocyte chemotactic proteins. J Neuroinflammation. 2015;12:237 pubmed publisher
    ..The number of MAC387+, CCR2+, CCR5+, and CD137+ cells in DRG tissue was quantified by immunohistochemistry...
  28. Chrul S, Polakowska E, Mycko M, Fendler W, Zwiech R, Szadkowska A. The effect of IL-2, IL-12 and IL15 on the function of natural killer cells in children suffering from type 1 diabetes mellitus. Pediatr Endocrinol Diabetes Metab. 2013;19:91-5 pubmed
    ..FACS analysis of cell surface antigens--CD16, CD56, NKG2D and CD137 was performed using LSR II flow cytometer...
  29. Kroon P, Gadiot J, Peeters M, Gasparini A, Deken M, Yagita H, et al. Concomitant targeting of programmed death-1 (PD-1) and CD137 improves the efficacy of radiotherapy in a mouse model of human BRAFV600-mutant melanoma. Cancer Immunol Immunother. 2016;65:753-63 pubmed publisher
    ..Tumor-bearing mice were treated with different combinations of immunomodulatory antibodies (?-CTLA-4, ?-PD-1, ?-CD137) or interleukin-2 (IL-2) alone or in combination with SBRT...
  30. Mimura K, Kua L, Shimasaki N, Shiraishi K, Nakajima S, Siang L, et al. Upregulation of thioredoxin-1 in activated human NK cells confers increased tolerance to oxidative stress. Cancer Immunol Immunother. 2017;66:605-613 pubmed publisher
    ..Collectively, these data document that activated NK cells can resist to H2O2-induced cell death by up-regulation of TXN1. ..
  31. Giardino Torchia M, Munitic I, Castro E, Herz J, McGavern D, Ashwell J. c-IAP ubiquitin protein ligase activity is required for 4-1BB signaling and CD8(+) memory T-cell survival. Eur J Immunol. 2015;45:2672-82 pubmed publisher
    ..Studies with T-cell adoptive transfer demonstrated that the enhanced decay of memory cells was T-cell intrinsic. Thus, c-IAP E3 activity is required for 4-1BB coreceptor signaling and maintenance of CD8(+) T-cell memory. ..
  32. Bartkowiak T, Singh S, Yang G, Galvan G, Haria D, Ai M, et al. Unique potential of 4-1BB agonist antibody to promote durable regression of HPV+ tumors when combined with an E6/E7 peptide vaccine. Proc Natl Acad Sci U S A. 2015;112:E5290-9 pubmed publisher
  33. Son Y, Kim B, Eo S, Park Y, Kim K. Dexamethasone Suppresses Oxysterol-Induced Differentiation of Monocytic Cells. Oxid Med Cell Longev. 2016;2016:2915382 pubmed publisher
    ..Increased levels of surface protein and transcription of CD105, CD137, and CD166 by treatment with 27OHChol were significantly inhibited by cotreatment with Dx...
  34. Yan J, Gong J, Liu P, Wang C, Chen G. Positive correlation between CD137 expression and complex stenosis morphology in patients with acute coronary syndromes. Clin Chim Acta. 2011;412:993-8 pubmed publisher
    b>CD137, a member of the tumor necrosis factor receptor superfamily, has been reported to be expressed highly in patients with acute coronary syndromes...
  35. Yan J, Yin Y, Zhong W, Wang C, Wang Z. CD137 Regulates NFATc1 Expression in Mouse VSMCs through TRAF6/NF-κB p65 Signaling Pathway. Mediators Inflamm. 2015;2015:639780 pubmed publisher
    Our previous study proved that CD137-CD137L interaction can regulate the expression of NFATc1. Here, we investigated whether CD137 signaling regulates the expression of NFATc1 in mice VSMCs through TRAF6/NF-κB p65 pathway...
  36. Curry W, Gorrepati R, Piesche M, Sasada T, Agarwalla P, Jones P, et al. Vaccination with Irradiated Autologous Tumor Cells Mixed with Irradiated GM-K562 Cells Stimulates Antitumor Immunity and T Lymphocyte Activation in Patients with Recurrent Malignant Glioma. Clin Cancer Res. 2016;22:2885-96 pubmed publisher
    ..Vaccination with irradiated autologous tumor cells mixed with GM-K562 cells is feasible, well tolerated, and active in patients with recurrent malignant glioma. Clin Cancer Res; 22(12); 2885-96. ©2016 AACR. ..
  37. Cheng Z, Wei R, Ma Q, Shi L, He F, Shi Z, et al. In Vivo Expansion and Antitumor Activity of Coinfused CD28- and 4-1BB-Engineered CAR-T Cells in Patients with B Cell Leukemia. Mol Ther. 2018;26:976-985 pubmed publisher
    ..These results confirm a feasible method of comparing different CAR designs within individual patients, potentially offering objective insights that may facilitate the development of optimal CAR-T cell-based immunotherapies. ..
  38. Vilgelm A, Johnson C, Prasad N, Yang J, Chen S, Ayers G, et al. Connecting the Dots: Therapy-Induced Senescence and a Tumor-Suppressive Immune Microenvironment. J Natl Cancer Inst. 2016;108:djv406 pubmed publisher
    ..response was queried in immunodeficient mice, in mice with CCL5-deficient tumors, and in mice cotreated with CD137 agonist to activate TILs...
  39. Engelstein R, Merims S, Eisenberg G, Cohen J, Frank S, Hamburger T, et al. Immune Monitoring of Patients Treated With a Whole-Cell Melanoma Vaccine Engineered to Express 4-1BBL. J Immunother. 2016;39:321-8 pubmed publisher
    ..The use of a costimulatory molecule as part of a vaccine confers a selective increase of T-cell subsets with antimelanoma reactivity, which in some cases were characterized for their epitope specificity. ..
  40. Li M, Guo R, Yu F, Chen X, Zhao H, Li H, et al. Indole-3-Acetic Acid Biosynthesis Pathways in the Plant-Beneficial Bacterium Arthrobacter pascens ZZ21. Int J Mol Sci. 2018;19: pubmed publisher
    ..IAM), indole-3-pyruvic acid (IPyA), and the enzymatic reduction product of the latter, indole-3-lactic acid (ILA), among the metabolites of ZZ21, and subsequently also IAM, ILA, and indole-3-ethanol (TOL), which is the enzymatic ..
  41. Turaj A, Cox K, Penfold C, French R, Mockridge C, Willoughby J, et al. Augmentation of CD134 (OX40)-dependent NK anti-tumour activity is dependent on antibody cross-linking. Sci Rep. 2018;8:2278 pubmed publisher
    ..It acts as a costimulatory receptor on T cells, but its role on NK cells is poorly understood. CD137, another TNFRSF member has been shown to enhance the anti-tumour activity of NK cells in various malignancies...
  42. Koristka S, Kegler A, Bergmann R, Arndt C, Feldmann A, Albert S, et al. Engrafting human regulatory T cells with a flexible modular chimeric antigen receptor technology. J Autoimmun. 2018;90:116-131 pubmed publisher
    ..In order to augment efficacy and safety, different intracellular signaling domains were tested. Both 4-1BB (CD137) and CD28 costimulation induced strong suppressive function of genetically modified Tregs...
  43. Waller E, McKinney N, Hicks R, Carmichael A, Sissons J, Wills M. Differential costimulation through CD137 (4-1BB) restores proliferation of human virus-specific "effector memory" (CD28(-) CD45RA(HI)) CD8(+) T cells. Blood. 2007;110:4360-6 pubmed
    ..with viral peptide presented by autologous monocytes, the virus-specific T cells show early up-regulation of CD137 (4-1BB) and CD278 (ICOS), re-express CD28, and proliferate with similarly high cloning efficiency in limiting ..
  44. Prado Garcia H, Romero Garcia S, Puerto Aquino A, Rumbo Nava U. The PD-L1/PD-1 pathway promotes dysfunction, but not "exhaustion", in tumor-responding T cells from pleural effusions in lung cancer patients. Cancer Immunol Immunother. 2017;66:765-776 pubmed publisher
    ..Remarkably, pleural effusion CD8+ T cells that responded to the tumor antigens MAGE-3A and WT-1 (identified as CD137+ cells) were lower in frequency than CMV pp65-responding CD8+ T cells and did not have an exhausted phenotype (PD-..
  45. Seliktar Ofir S, Merhavi Shoham E, Itzhaki O, Yunger S, Markel G, Schachter J, et al. Selection of Shared and Neoantigen-Reactive T Cells for Adoptive Cell Therapy Based on CD137 Separation. Front Immunol. 2017;8:1211 pubmed publisher
    ..b>CD137 (4-1BB) has been identified as a co-stimulatory marker, which is induced upon the specific interaction of T cells ..
  46. Munoz Bendix C, Beseoglu K, Kram R. Extracorporeal decarboxylation in patients with severe traumatic brain injury and ARDS enables effective control of intracranial pressure. Crit Care. 2015;19:381 pubmed publisher
    ..Pumpless extracorporeal lung assist (pECLA) devices (iLA Membrane Ventilator; Novalung, Heilbronn, Germany) can improve decarboxylation without aggravation associated with ..
  47. Wang L, Yi Y, Yin D, Zhou Z, Fan J, Ye W, et al. Augmented CD3(+)CD8(+) and CD3(+)CD56(-) cells in cytokine-induced killer cells cultured with engineered cells for costimulatory enhancement from heavily pretreated patients with solid tumor. Cytotherapy. 2016;18:581-9 pubmed publisher
    ..This study suggests that ECCE may improve the efficacy of CIKs therapy and make CIKs therapy possible for the patients whose CIKs would be hard to be cultured using conventional methods. ..
  48. Nagila A, Netsawang J, Suttitheptumrong A, Morchang A, Khunchai S, Srisawat C, et al. Inhibition of p38MAPK and CD137 signaling reduce dengue virus-induced TNF-? secretion and apoptosis. Virol J. 2013;10:105 pubmed publisher
    ..The p38 MAPK activation and TNF-? production were controlled by p38 MAPK and CD137 signaling in DENV-infected HepG2 cells as activated p38 MAPK, TNF-? and apoptosis were significantly decreased in ..
  49. Das A, McDonald D, Lowe S, Bredlau A, Vanek K, Patel S, et al. Immunological low-dose radiation modulates the pediatric medulloblastoma antigens and enhances antibody-dependent cellular cytotoxicity. Childs Nerv Syst. 2017;33:429-436 pubmed publisher
    ..Several of these HLA subtypes, such as MAGE C1, CD137, and ICAM-1, have demonstrated upregulation...
  50. Parray H, Lone J, Park J, Choi J, Yun J. Magnolol promotes thermogenesis and attenuates oxidative stress in 3T3-L1 adipocytes. Nutrition. 2018;50:82-90 pubmed publisher
    ..Magnolol significantly enhanced expression of a core set of brown fat-specific marker genes (Ucp1, Cd137, Prdm16, Cidea, and Tbx1) and proteins (UCP1, PRDM16, and PGC-1α)...
  51. Schwarz H, Tuckwell J, Lotz M. A receptor induced by lymphocyte activation (ILA): a new member of the human nerve-growth-factor/tumor-necrosis-factor receptor family. Gene. 1993;134:295-8 pubmed
    ..The gene encodes three cysteine-rich motifs in the extracellular domain which are characteristic of this receptor family, a transmembrane region and a short N-terminal cytoplasmic portion which contains potential phosphorylation sites. ..
  52. Chen Y, Bangash A, Song J, Zhong W, Wang C, Shao C, et al. Activation of CD137 signaling accelerates vascular calcification in vivo and vitro. Int J Cardiol. 2017;230:198-203 pubmed publisher
    ..b>CD137 signaling has previously shown to be involved in atherosclerosis...
  53. Hung A, Garzon Muvdi T, Lim M. Biomarkers and Immunotherapeutic Targets in Glioblastoma. World Neurosurg. 2017;102:494-506 pubmed publisher
    ..studied examples include cytokines (IL-4, IL-13, and TGF-?), checkpoint molecules (PD-1, CTLA-4, TIM-3, LAG-3, CD137, GITR, OX40), and growth/angiogenesis proteins (endoglin and EGFR)...
  54. Leibman R, Richardson M, Ellebrecht C, Maldini C, Glover J, Secreto A, et al. Supraphysiologic control over HIV-1 replication mediated by CD8 T cells expressing a re-engineered CD4-based chimeric antigen receptor. PLoS Pathog. 2017;13:e1006613 pubmed publisher
    ..Together, these data indicate that potent HIV-specific T cells can be generated using improved CAR design and that CAR T cells could be important components of an HIV cure strategy...
  55. Zhang Y, Li N, Suh H, Irvine D. Nanoparticle anchoring targets immune agonists to tumors enabling anti-cancer immunity without systemic toxicity. Nat Commun. 2018;9:6 pubmed publisher
    Immunostimulatory agents such as agonistic anti-CD137 and interleukin (IL)-2 generate effective anti-tumor immunity but also elicit serious toxicities, hampering their clinical application...
  56. Cepowicz D, Gryko M, Zaręba K, Stasiak Bermuta A, Kędra B. Assessment of activity of an adhesion molecule CD134 and CD137 in colorectal cancer patients. Pol Przegl Chir. 2011;83:641-5 pubmed publisher
    ..THE AIM OF THE STUDY was to determine expression of adhesion molecules CD134 and CD137 in the peripheral blood in colorectal cancer patients, depending on clinical cancer stage, size and invasion of ..
  57. Miller C, Yang J, England E, Yin A, Baile C, Rayalam S. Isoproterenol Increases Uncoupling, Glycolysis, and Markers of Beiging in Mature 3T3-L1 Adipocytes. PLoS ONE. 2015;10:e0138344 pubmed publisher
    ..Lastly, markers of beige adipocytes (protein content of CD137 and gene transcript of CITED1) were also found to be upregulated at 48 hours of isoproterenol treatment...
  58. Kim B, Kim J, Kim E, Lee J, Joo D, Huh K, et al. Role of Thalidomide on the Expression of OX40, 4-1BB, and GITR in T Cell Subsets. Transplant Proc. 2016;48:1270-4 pubmed publisher
    ..Considering these results, TM may have an immune modulatory role through the T cell subset-specific change of OX40, 4-1BB, and GITR expression. Further study is required to elucidate the effect of thalidomide on T cells. ..
  59. Chen C, Li K, Jiang H, Song F, Gao H, Pan X, et al. Development of T cells carrying two complementary chimeric antigen receptors against glypican-3 and asialoglycoprotein receptor 1 for the treatment of hepatocellular carcinoma. Cancer Immunol Immunother. 2017;66:475-489 pubmed publisher
    ..Together, T cells carrying two complementary CARs against GPC3 and ASGR1 may reduce the risk of on-target, off-tumor toxicity while maintaining relatively potent antitumor activities on GPC3+ASGR1+ HCC. ..
  60. Ma Z, Liu G, Zhang M, Li M, Liu Y, Yanfang J. Helicobacter pylori Infection Increases Frequency of PDCA-1(+) (CD317(+)) B-cell Subsets. Arch Med Res. 2016;47:96-104 pubmed publisher
    ..of PDCA-1(+) B cells, PDCA-1(+)IgM(+) B cells, CD93(+)PDCA-1(+) B cells, CD93(+)PDCA-1(+)IgM(+) B cells, CD137(+)PDCA-1(+) B cells and CD137(+)PDCA-1(+)IgM(+) B cells were detected in patients with H...
  61. Van Blarcom T, Lindquist K, Melton Z, Cheung W, Wagstrom C, McDonough D, et al. Productive common light chain libraries yield diverse panels of high affinity bispecific antibodies. MAbs. 2017;: pubmed publisher
    ..This approach allowed us to identify antibodies with a wide range of agonistic activity that are being used to further investigate the therapeutic potential of antibodies targeting one or more epitopes of 4-1BB...
  62. Hebb J, Mosley A, Vences Catalan F, Rajasekaran N, Rosén A, Ellmark P, et al. Administration of low-dose combination anti-CTLA4, anti-CD137, and anti-OX40 into murine tumor or proximal to the tumor draining lymph node induces systemic tumor regression. Cancer Immunol Immunother. 2018;67:47-60 pubmed publisher
    ..Here, we test this concept using the novel combination of immunomodulators anti-CTLA4, -CD137, and -OX40...
  63. Brown C, Aguilar B, Starr R, Yang X, Chang W, Weng L, et al. Optimization of IL13Rα2-Targeted Chimeric Antigen Receptor T Cells for Improved Anti-tumor Efficacy against Glioblastoma. Mol Ther. 2018;26:31-44 pubmed publisher
    ..Here, we describe the optimization of IL13Rα2-targeted CAR T cells, including the design of a 4-1BB (CD137) co-stimulatory CAR (IL13BBζ) and a manufacturing platform using enriched central memory T cells...
  64. Lu Z, Condomines M, Tarte K, Nadal L, Delteil M, Rossi J, et al. B7-1 and 4-1BB ligand expression on a myeloma cell line makes it possible to expand autologous tumor-specific cytotoxic T cells in vitro. Exp Hematol. 2007;35:443-53 pubmed
    ..It permitted the long-term expansion of autologous anti-tumor CTL with a shared anti-MMC repertoire, for one HMCL. These data suggest developing an immunotherapy using modified tumor cells in patients with multiple myeloma. ..
  65. Carpenito C, Milone M, Hassan R, Simonet J, Lakhal M, Suhoski M, et al. Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains. Proc Natl Acad Sci U S A. 2009;106:3360-5 pubmed publisher
    ..fragment that binds mesothelin and that is fused to signaling domains derived from T-cell receptor zeta, CD28, and CD137 (4-1BB)...
  66. Chacon J, Wu R, Sukhumalchandra P, Molldrem J, Sarnaik A, Pilon Thomas S, et al. Co-stimulation through 4-1BB/CD137 improves the expansion and function of CD8(+) melanoma tumor-infiltrating lymphocytes for adoptive T-cell therapy. PLoS ONE. 2013;8:e60031 pubmed publisher
    ..In this study, we determined the effects of activating the TNF-R family member 4-1BB/CD137, specifically induced in activated CD8(+) T cells, on the yield, phenotype, and functional activity of expanded ..
  67. Ambrosio L, Wang J, Gouesbet G. On the validity of the integral localized approximation for Bessel beams and associated radiation pressure forces. Appl Opt. 2017;56:5377-5387 pubmed publisher
    In this paper we investigate the integral version of the localized approximation (ILA)-a powerful technique for evaluating the beam shape coefficients in the framework of the generalized Lorenz-Mie theory-as applied to ideal scalar ..
  68. Marcucci F, Rumio C, Corti A. Tumor cell-associated immune checkpoint molecules - Drivers of malignancy and stemness. Biochim Biophys Acta Rev Cancer. 2017;1868:571-583 pubmed publisher
    ..have also been shown to induce the acquisition of malignant traits, such as PD-1, B7-H3, B7-H4, Tim-3, CD70, CD28, CD137, CD40 and CD47...
  69. Priceman S, Tilakawardane D, Jeang B, Aguilar B, Murad J, Park A, et al. Regional Delivery of Chimeric Antigen Receptor-Engineered T Cells Effectively Targets HER2+ Breast Cancer Metastasis to the Brain. Clin Cancer Res. 2018;24:95-105 pubmed publisher
    ..i>Clin Cancer Res; 24(1); 95-105. ©2017 AACR. ..
  70. Chester C, Sanmamed M, Wang J, Melero I. Immunotherapy targeting 4-1BB: mechanistic rationale, clinical results, and future strategies. Blood. 2017;: pubmed publisher
    4-1BB (CD137, TNFRSF9) is an inducible costimulatory receptor expressed on activated T and natural killer (NK) cells...
  71. Laderach D, Movassagh M, Johnson A, Mittler R, Galy A. 4-1BB co-stimulation enhances human CD8(+) T cell priming by augmenting the proliferation and survival of effector CD8(+) T cells. Int Immunol. 2002;14:1155-67 pubmed
    ..As 4-1BB triggering could be protracted from the TCR signal, 4-1BB agonists may function through these mechanisms to enhance or rescue suboptimal immune responses. ..
  72. Cole S, Benam K, McMichael A, Ho L. Involvement of the 4-1BB/4-1BBL pathway in control of monocyte numbers by invariant NKT cells. J Immunol. 2014;192:3898-907 pubmed publisher
    ..4-1BB/L costimulation amplified monocyte-mediated proliferation of iNKT cells, indirectly providing a method for monocytes to control their own numbers during infection. ..
  73. Zhao S, Xing Y, Natkunam Y. Use of CD137 ligand expression in the detection of small B-cell lymphomas involving the bone marrow. Hum Pathol. 2014;45:1024-30 pubmed publisher
    ..We recently described the hematopoietic tissue distribution patterns of CD137 and CD137 ligand (CD137L), which have shown promise as immunotherapeutic targets...
  74. Payne T, Blackinton J, Frisbee A, Pickeral J, Sawant S, Vandergrift N, et al. Transcriptional and posttranscriptional regulation of cytokine gene expression in HIV-1 antigen-specific CD8+ T cells that mediate virus inhibition. J Virol. 2014;88:9514-28 pubmed publisher
    ..and MIP-1?; granulocyte-macrophage colony-stimulating factor (GM-CSF); lymphotactin (XCL1); tumor necrosis factor receptor superfamily member 9 (TNFRSF9); and gamma interferon (IFN-?)...
  75. Madireddi S, Eun S, Lee S, Nemčovičová I, Mehta A, Zajonc D, et al. Galectin-9 controls the therapeutic activity of 4-1BB-targeting antibodies. J Exp Med. 2014;211:1433-48 pubmed publisher
    ..Antibodies to 4-1BB (CD137) are currently in clinical trials and can both augment immunity in cancer and promote regulatory T cells that ..
  76. Benaduce A, Brenneman R, Schrand B, Pollack A, Gilboa E, Ishkanian A. 4-1BB Aptamer-Based Immunomodulation Enhances the Therapeutic Index of Radiation Therapy in Murine Tumor Models. Int J Radiat Oncol Biol Phys. 2016;96:458-461 pubmed publisher
    ..4-1BB aptamer-based costimulation affords a comparable and less toxic strategy to augment RT-mediated tumor control. ..
  77. Yan Z, Zheng X, Yi L, Wang J, Wang X, Wei P, et al. CD137 is a Useful Marker for Identifying CD4+ T Cell Responses to Mycobacterium tuberculosis. Scand J Immunol. 2017;85:372-380 pubmed publisher
    Upregulation of CD137 on recently activated CD8+ T cells has been used to identify rare viral and tumour antigen-specific T cells from the peripheral blood...
  78. Mbanwi A, Lin G, Wang K, Watts T. Constitutive interaction between 4-1BB and 4-1BBL on murine LPS-activated bone marrow dendritic cells masks detection of 4-1BBL by TKS-1 but not 19H3 antibody. J Immunol Methods. 2017;450:81-89 pubmed publisher
    ..These data suggest that 19H3 is the preferable antibody to use to detect 4-1BBL in the presence of its receptor. ..
  79. Kang S, Lee S, Park S, Kim J, Kim H, Lee H, et al. Anti-CD137 Suppresses Tumor Growth by Blocking Reverse Signaling by CD137 Ligand. Cancer Res. 2017;77:5989-6000 pubmed publisher
    b>CD137 (4-1BB) is a T-cell costimulatory molecule, and agonstic CD137 antibodies are currently being evaluated in the clinic as cancer immunotherapy...
  80. Schwarz H, Arden K, Lotz M. 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. Biochem Biophys Res Commun. 1997;235:699-703 pubmed
    b>CD137 (ILA/4-1BB) is a member of the tumor-necrosis-factor receptor family...
  81. Teijeira A, Palazon A, Garasa S, Marre D, Auba C, Rogel A, et al. CD137 on inflamed lymphatic endothelial cells enhances CCL21-guided migration of dendritic cells. FASEB J. 2012;26:3380-92 pubmed publisher
    b>CD137/TNFR9/41BB was originally described as a surface molecule present on activated T and NK cells...
  82. Fernández Do Porto D, Auzmendi J, Peña D, Garcia V, Moffatt L. Bayesian approach to model CD137 signaling in human M. tuberculosis in vitro responses. PLoS ONE. 2013;8:e55987 pubmed publisher
    ..Among them, the CD137:CD137L pathway is known to modulate innate and adaptive human responses against Mycobacterium tuberculosis...
  83. Joseph A, Srivastava R, Zabaleta J, Davila E. Cross-talk between 4-1BB and TLR1-TLR2 Signaling in CD8+ T Cells Regulates TLR2's Costimulatory Effects. Cancer Immunol Res. 2016;4:708-16 pubmed publisher
    ..Cancer Immunol Res; 4(8); 708-16. ©2016 AACR. ..
  84. van Nierop G, van Luijn M, Michels S, Melief M, Janssen M, Langerak A, et al. Phenotypic and functional characterization of T cells in white matter lesions of multiple sclerosis patients. Acta Neuropathol. 2017;134:383-401 pubmed publisher
    ..cells expressing a cytotoxic effector phenotype (CD95L and granzyme B) indicative for local antigenic stimulation (CD137)...
  85. Lee S, Olsen P, Lee D, Kenoyer A, Budde L, O Steen S, et al. Preclinical Optimization of a CD20-specific Chimeric Antigen Receptor Vector and Culture Conditions. J Immunother. 2017;: pubmed publisher
    ..These results provide the basis for clinical testing of a lentiviral construct encoding a fully human CD20-targeted CAR with CD28 and 4-1BB costimulatory domains and truncated CD19 (tCD19) transduction marker...
  86. Zhou Z, Kim S, Hurtado J, Lee Z, Kim K, Pollok K, et al. Characterization of human homologue of 4-1BB and its ligand. Immunol Lett. 1995;45:67-73 pubmed
    ..Daudi, a B-cell lymphoma, was one of the B-cell lines that carried a higher number of ligands. Scatchard analysis showed that the Kd = 1.4 x 10(9) M and the number of ligands in Daudi cell was 4.2 x 10(3). ..
  87. Reali C, Curto M, Sogos V, Scintu F, Pauly S, Schwarz H, et al. Expression of CD137 and its ligand in human neurons, astrocytes, and microglia: modulation by FGF-2. J Neurosci Res. 2003;74:67-73 pubmed
    b>CD137 (ILA, 4-1BB), a member of the tumor necrosis factor receptor family, and its ligand CD137-L were assayed by RT-PCR and immunocytochemistry in cultured human brain cells...
  88. Ghosh A, Smith M, James S, DAVILA M, Velardi E, Argyropoulos K, et al. Donor CD19 CAR T cells exert potent graft-versus-lymphoma activity with diminished graft-versus-host activity. Nat Med. 2017;23:242-249 pubmed publisher
    ..In contrast, first-generation and 4-1BB-costimulated CAR T cells increased the occurrence of GVHD. These findings could explain the reduced risk of GVHD occurring with cumulative TCR and CAR signaling. ..
  89. Dushyanthen S, Teo Z, Caramia F, Savas P, Mintoff C, Virassamy B, et al. Agonist immunotherapy restores T cell function following MEK inhibition improving efficacy in breast cancer. Nat Commun. 2017;8:606 pubmed publisher
    ..Here the authors show that TILs activity following MEK inhibition can be enhanced by agonist immunotherapy resulting in synergic therapeutic effects. ..
  90. Aznar M, Labiano S, Díaz Lagares A, Molina C, Garasa S, Azpilikueta A, et al. CD137 (4-1BB) Costimulation Modifies DNA Methylation in CD8+ T Cell-Relevant Genes. Cancer Immunol Res. 2018;6:69-78 pubmed publisher
    b>CD137 (4-1BB) costimulation imprints long-term changes that instruct the ultimate behavior of T cells that have previously experienced CD137 ligation. Epigenetic changes could provide a suitable mechanism for these long-term consequences...
  91. Lone J, Parray H, Yun J. Nobiletin induces brown adipocyte-like phenotype and ameliorates stress in 3T3-L1 adipocytes. Biochimie. 2018;146:97-104 pubmed publisher
    ..Nobiletin treatment rapidly elevated the expression levels of beige-specific genes such as Cd137, Cidea, Tbx1, and Tmem26...
  92. Kim Y, Han M, Broxmeyer H. 4-1BB regulates NKG2D costimulation in human cord blood CD8+ T cells. Blood. 2008;111:1378-86 pubmed
    ..Co-expression of NKG2D and 4-1BB may represent an important biomarker for defining competency of tumor infiltrating CD8(+) T cells. ..