Tumor necrosis factor receptor-2 (TNFR2): an overview of an emerging drug target

References

• Wajant H, Pfizenmaier K, Scheurich P. Tumor necrosis factor signaling. Cell Death Differ. 2003;10:45–65.
   PubMed Web of Science ®Google Scholar
• Bodmer JL, Schneider P, Tschopp J. The molecular architecture of the TNF superfamily. Trends Biochem Sci. 2002;27:19–26.
   PubMed Web of Science ®Google Scholar
• Locksley RM, Killeen N, Lenardo MJ. The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell. 2001;104:487–501.
   PubMed Web of Science ®Google Scholar
• Pegoretti V, Baron W, Laman JD, et al. Selective modulation of TNF-TNFRs signaling: insights for multiple sclerosis treatment. Front Immunol. 2018;9:925.
   PubMed Web of Science ®Google Scholar
• Al-Lamki RS, Lu W, Wang J, et al. TNF, acting through inducibly expressed TNFR2, drives activation and cell cycle entry of c-Kit+ cardiac stem cells in ischemic heart disease. Stem Cells. 2013;31:1881–1892.
   PubMed Web of Science ®Google Scholar
• Nan J, Hu H, Sun Y, et al. TNFR2 stimulation promotes mitochondrial fusion via Stat3- and NF-kB-dependent activation of OPA1 expression. Circ Res. 2017;121:392–410.
   PubMed Web of Science ®Google Scholar
• Candel S, de Oliveira S, Lopez-Munoz A, et al. Tnfa signaling through tnfr2 protects skin against oxidative stress-induced inflammation. PLoS Biol. 2014;12:e1001855.
   PubMed Web of Science ®Google Scholar
• Wajant H. The role of TNF in cancer. Results Probl Cell Differ. 2009;49:1–15.
   PubMedGoogle Scholar
• Fischer R, Wajant H, Kontermann R, et al. Astrocyte-specific activation of TNFR2 promotes oligodendrocyte maturation by secretion of leukemia inhibitory factor. Glia. 2014;62:272–283.
   PubMed Web of Science ®Google Scholar
• Patel JR, Williams JL, Muccigrosso MM, et al. Astrocyte TNFR2 is required for CXCL12-mediated regulation of oligodendrocyte progenitor proliferation and differentiation within the adult CNS. Acta Neuropathol. 2012;124:847–860.
   PubMed Web of Science ®Google Scholar
• Maney NJ, Reynolds G, Krippner-Heidenreich A, et al. Dendritic cell maturation and survival are differentially regulated by TNFR1 and TNFR2. J Immunol. 2014;193:4914–4923.
   PubMed Web of Science ®Google Scholar
• Zhang R, Xu Y, Ekman N, et al. Etk/Bmx transactivates vascular endothelial growth factor 2 and recruits phosphatidylinositol 3-kinase to mediate the tumor necrosis factor-induced angiogenic pathway. J Biol Chem. 2003;278:51267–51276.
   PubMed Web of Science ®Google Scholar
• Mizoguchi E, Mizoguchi A, Takedatsu H, et al. Role of tumor necrosis factor receptor 2 (TNFR2) in colonic epithelial hyperplasia and chronic intestinal inflammation in mice. Gastroenterology. 2002;122:134–144.
   PubMed Web of Science ®Google Scholar
• Grell M, Becke FM, Wajant H, et al. Tumor necrosis factor (TNF) receptor type 2 mediates thymocyte proliferation independently of TNF receptor type 1. Eur J Immunol. 1998;28:257–263.
   PubMed Web of Science ®Google Scholar
• Heck S, Nguyen J, Le DD, et al. Pharmacological therapy of bronchial asthma: the role of biologicals. Int Arch Allergy Immunol. 2015;168:241–252.
   PubMed Web of Science ®Google Scholar
• Feldman AM, McTiernan C. Is there any future for tumor necrosis factor antagonists in chronic heart failure? Am J Cardiovasc Drugs. 2004;4:11–19.
   PubMedGoogle Scholar
• Shanmugam VK, Zaman NM, McNish S, et al. Review of current immunologic therapies for hidradenitis suppurativa. Int J Rheumatol. 2017;2017:8018192.
   PubMedGoogle Scholar
• Kemanetzoglou E, Andreadou E. CNS demyelination with TNF-alpha blockers. Curr Neurol Neurosci Rep. 2017;17:36.
   PubMed Web of Science ®Google Scholar
• Abraham E, Laterre PF, Garbino J, et al. Lenercept (p55 tumor necrosis factor receptor fusion protein) in severe sepsis and early septic shock: a randomized, double-blind, placebo-controlled, multicenter phase III trial with 1,342 patients. Crit Care Med. 2001;29:503–510.
   PubMed Web of Science ®Google Scholar
• Bernard GR, Francois B, Mira JP, et al. Evaluating the efficacy and safety of two doses of the polyclonal anti-tumor necrosis factor-alpha fragment antibody AZD9773 in adult patients with severe sepsis and/or septic shock: randomized, double-blind, placebo-controlled phase IIb study*. Crit Care Med. 2014;42:504–511.
   PubMed Web of Science ®Google Scholar
• Choi SW, Reddy P. Current and emerging strategies for the prevention of graft-versus-host disease. Nat Rev Clin Oncol. 2014;11:536–547.
   PubMed Web of Science ®Google Scholar
• Zhu LJ, Yang X, Yu XQ. Anti-TNF-alpha therapies in systemic lupus erythematosus. J Biomed Biotechnol. 2010;2010:465898.
   PubMedGoogle Scholar
• Brenner D, Blaser H, Mak TW. Regulation of tumour necrosis factor signalling: live or let die. Nat Rev Immunol. 2015;15:362–374.
   PubMed Web of Science ®Google Scholar
• Kotyla PJ. Bimodal function of anti-TNF treatment: shall we be concerned about anti-TNF treatment in patients with rheumatoid arthritis and heart failure?. Int J Mol Sci. 2018;19.
   Web of Science ®Google Scholar
• Zhang HG, Liu C, Su K, et al. A membrane form of TNF-alpha presented by exosomes delays T cell activation-induced cell death. J Immunol. 2006;176:7385–7393.
   PubMed Web of Science ®Google Scholar
• Soderberg A, Barral AM, Soderstrom M, et al. Redox-signaling transmitted in trans to neighboring cells by melanoma-derived TNF-containing exosomes. Free Radic Biol Med. 2007;43:90–99.
   PubMed Web of Science ®Google Scholar
• Munich S, Sobo-Vujanovic A, Buchser WJ, et al. Dendritic cell exosomes directly kill tumor cells and activate natural killer cells via TNF superfamily ligands. Oncoimmunology. 2012;1:1074–1083.
   PubMed Web of Science ®Google Scholar
• TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study. The lenercept multiple sclerosis study group and The University of British Columbia MS/MRI analysis group. Neurology. 1999;53:457–465.
   PubMedGoogle Scholar
• McCann FE, Perocheau DP, Ruspi G, et al. Selective tumor necrosis factor receptor I blockade is antiinflammatory and reveals immunoregulatory role of tumor necrosis factor receptor II in collagen-induced arthritis. Arthritis Rheumatol. 2014;66:2728–2738.
   PubMed Web of Science ®Google Scholar
• Kim EY, Teh HS. TNF type 2 receptor (p75) lowers the threshold of T cell activation. J Immunol. 2001;167:6812–6820.
   PubMed Web of Science ®Google Scholar
• Kim EY, Priatel JJ, Teh SJ, et al. TNF receptor type 2 (p75) functions as a costimulator for antigen-driven T cell responses in vivo. J Immunol. 2006;176:1026–1035.
   PubMed Web of Science ®Google Scholar
• Wortzman ME, Lin GHY, Watts TH, et al. Intrinsic TNF/TNFR2 interactions fine-tune the CD8 T cell response to respiratory influenza virus infection in mice. PLoS One. 2013;8:e68911.
   PubMed Web of Science ®Google Scholar
• Suresh M, Singh A, Fischer C. Role of tumor necrosis factor receptors in regulating CD8 T-cell responses during acute lymphocytic choriomeningitis virus infection. J Virol. 2005;79:202–213.
   PubMed Web of Science ®Google Scholar
• Richter MV, Topham DJ. The alpha1beta1 integrin and TNF receptor II protect airway CD8+ effector T cells from apoptosis during influenza infection. J Immunol. 2007;179:5054–5063.
   PubMed Web of Science ®Google Scholar
• Aravena O, Pesce B, Soto L, et al. Anti-TNF therapy in patients with rheumatoid arthritis decreases Th1 and Th17 cell populations and expands IFN-gamma-producing NK cell and regulatory T cell subsets. Immunobiology. 2011;216:1256–1263.
   PubMed Web of Science ®Google Scholar
• Ehrenstein MR, Evans JG, Singh A, et al. Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy. J Exp Med. 2004;200:277–285.
   PubMed Web of Science ®Google Scholar
• Valencia X, Stephens G, Goldbach-Mansky R, et al. TNF downmodulates the function of human CD4+CD25hi T-regulatory cells. Blood. 2006;108:253–261.
   PubMed Web of Science ®Google Scholar
• Nie H, Zheng Y, Li R, et al. Phosphorylation of FOXP3 controls regulatory T cell function and is inhibited by TNF-alpha in rheumatoid arthritis. Nat Med. 2013;19:322–328.
   PubMed Web of Science ®Google Scholar
• Chee J, Angstetra E, Mariana L, et al. TNF receptor 1 deficiency increases regulatory T cell function in nonobese diabetic mice. J Immunol. 2011;187:1702–1712.
   PubMed Web of Science ®Google Scholar
• Wu AJ, Hua H, Munson SH, et al. Tumor necrosis factor-alpha regulation of CD4+CD25+ T cell levels in NOD mice. Proc Natl Acad Sci U S A. 2002;99:12287–12292.
   PubMed Web of Science ®Google Scholar
• Chen X, Baumel M, Mannel DN, et al. Interaction of TNF with TNF receptor type 2 promotes expansion and function of mouse CD4+CD25+ T regulatory cells. J Immunol. 2007;179:154–161.
   PubMed Web of Science ®Google Scholar
• Chen X, Subleski JJ, Hamano R, et al. Co-expression of TNFR2 and CD25 identifies more of the functional CD4+FOXP3+ regulatory T cells in human peripheral blood. Eur J Immunol. 2010;40:1099–1106.
   PubMed Web of Science ®Google Scholar
• Chen X, Subleski JJ, Kopf H, et al. Cutting edge: expression of TNFR2 defines a maximally suppressive subset of mouse CD4+CD25+FoxP3+ T regulatory cells: applicability to tumor-infiltrating T regulatory cells. J Immunol. 2008;180:6467–6471.
   PubMed Web of Science ®Google Scholar
• Zhang Q, Cui F, Fang L, et al. TNF-alpha impairs differentiation and function of TGF-beta-induced Treg cells in autoimmune diseases through Akt and Smad3 signaling pathway. J Mol Cell Biol. 2013;5:85–98.
   PubMed Web of Science ®Google Scholar
• Joedicke JJ, Myers L, Carmody AB, et al. Activated CD8+ T cells induce expansion of Vbeta5+ regulatory T cells via TNFR2 signaling. J Immunol. 2014;193:2952–2960.
   PubMed Web of Science ®Google Scholar
• Schmid T, Falter L, Weber S, et al. Chronic Inflammation Increases the Sensitivity of Mouse Treg for TNFR2 Costimulation. Front Immunol. 2017;8:1471.
   PubMed Web of Science ®Google Scholar
• Nie Y, He J, Shirota H, et al. Blockade of TNFR2 signaling enhances the immunotherapeutic effect of CpG ODN in a mouse model of colon cancer. Sci Signal. 2018;11.
   PubMed Web of Science ®Google Scholar
• Leclerc M, Naserian S, Pilon C, et al. Control of GVHD by regulatory T cells depends on TNF produced by T cells and TNFR2 expressed by regulatory T cells. Blood. 2016;128:1651–1659.
   PubMed Web of Science ®Google Scholar
• Zhao X, Rong L, Zhao X, et al. TNF signaling drives myeloid-derived suppressor cell accumulation. J Clin Invest. 2012;122:4094–4104.
   PubMed Web of Science ®Google Scholar
• Hu X, Li B, Li X, et al. Transmembrane TNF-alpha promotes suppressive activities of myeloid-derived suppressor cells via TNFR2. J Immunol. 2014;192:1320–1331.
   PubMed Web of Science ®Google Scholar
• Ba H, Li B, Li X, et al. Transmembrane tumor necrosis factor-alpha promotes the recruitment of MDSCs to tumor tissue by upregulating CXCR4 expression via TNFR2. Int Immunopharmacol. 2017;44:143–152.
   PubMed Web of Science ®Google Scholar
• Polz J, Remke A, Weber S, et al. Myeloid suppressor cells require membrane TNFR2 expression for suppressive activity. Immun Inflamm Dis. 2014;2:121–130.
   PubMedGoogle Scholar
• Ticha O, Moos L, Wajant H, et al. Expression of tumor necrosis factor receptor 2 characterizes TLR9-driven formation of interleukin-10-producing B Cells. Front Immunol. 2017;8:1951.
   PubMed Web of Science ®Google Scholar
• Eugster HP, Frei K, Bachmann R, et al. Severity of symptoms and demyelination in MOG-induced EAE depends on TNFR1. Eur J Immunol. 1999;29:626–632.
   PubMed Web of Science ®Google Scholar
• Suvannavejh GC, Lee HO, Padilla J, et al. Divergent roles for p55 and p75 tumor necrosis factor receptors in the pathogenesis of MOG(35-55)-induced experimental autoimmune encephalomyelitis. Cell Immunol. 2000;205:24–33.
   PubMed Web of Science ®Google Scholar
• Hovelmeyer N, Hao Z, Kranidioti K, et al. Apoptosis of oligodendrocytes via Fas and TNF-R1 is a key event in the induction of experimental autoimmune encephalomyelitis. J Immunol. 2005;175:5875–5884.
   PubMed Web of Science ®Google Scholar
• Habbas S, Santello M, Becker D, et al. Neuroinflammatory TNFalpha impairs memory via astrocyte signaling. Cell. 2015;163:1730–1741.
   PubMed Web of Science ®Google Scholar
• Tsakiri N, Papadopoulos D, Denis MC, et al. TNFR2 on non-haematopoietic cells is required for Foxp3+ Treg-cell function and disease suppression in EAE. Eur J Immunol. 2012;42:403–412.
   PubMed Web of Science ®Google Scholar
• Arnett HA, Mason J, Marino M, et al. TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination. Nat Neurosci. 2001;4:1116–1122.
   PubMed Web of Science ®Google Scholar
• Atretkhany KN, Mufazalov IA, Dunst J, et al. Intrinsic TNFR2 signaling in T regulatory cells provides protection in CNS autoimmunity. Proc Natl Acad Sci U S A. 2018;115:13051–13056.
   PubMed Web of Science ®Google Scholar
• Gao H, Danzi MC, Choi CS, et al. Opposing functions of microglial and macrophagic TNFR2 in the pathogenesis of experimental autoimmune encephalomyelitis. Cell Rep. 2017;18:198–212.
   PubMed Web of Science ®Google Scholar
• Madsen PM, Motti D, Karmally S, et al. Oligodendroglial TNFR2 mediates membrane TNF-dependent repair in experimental autoimmune encephalomyelitis by promoting oligodendrocyte differentiation and remyelination. J Neurosci. 2016;36:5128–5143.
   PubMed Web of Science ®Google Scholar
• Nomura T, Abe Y, Kamada H, et al. Therapeutic effect of PEGylated TNFR1-selective antagonistic mutant TNF in experimental autoimmune encephalomyelitis mice. J Control Release. 2011;149:8–14.
   PubMed Web of Science ®Google Scholar
• Williams SK, Maier O, Fischer R, et al. Antibody-mediated inhibition of TNFR1 attenuates disease in a mouse model of multiple sclerosis. PLoS One. 2014;9:e90117.
   PubMed Web of Science ®Google Scholar
• Steeland S, Van Ryckeghem S, Van Imschoot G, et al. TNFR1 inhibition with a Nanobody protects against EAE development in mice. Sci Rep. 2017;7:13646.
   PubMed Web of Science ®Google Scholar
• Dong Y, Fischer R, Naude PJ, et al. Essential protective role of tumor necrosis factor receptor 2 in neurodegeneration. Proc Natl Acad Sci U S A. 2016;113:12304–12309.
   PubMed Web of Science ®Google Scholar
• Levine B, Kalman J, Mayer L, et al. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med. 1990;323:236–241.
   PubMed Web of Science ®Google Scholar
• Kubota T, McTiernan CF, Frye CS, et al. Dilated cardiomyopathy in transgenic mice with cardiac-specific overexpression of tumor necrosis factor-alpha. Circ Res. 1997;81:627–635.
   PubMed Web of Science ®Google Scholar
• Bryant D, Becker L, Richardson J, et al. Cardiac failure in transgenic mice with myocardial expression of tumor necrosis factor-alpha. Circulation. 1998;97:1375–1381.
   PubMed Web of Science ®Google Scholar
• Sivasubramanian N, Coker ML, Kurrelmeyer KM, et al. Left ventricular remodeling in transgenic mice with cardiac restricted overexpression of tumor necrosis factor. Circulation. 2001;104:826–831.
   PubMed Web of Science ®Google Scholar
• Ntari L, Sakkou M, Chouvardas P, et al. Comorbid TNF-mediated heart valve disease and chronic polyarthritis share common mesenchymal cell-mediated aetiopathogenesis. Ann Rheum Dis. 2018;77:926–934.
   PubMed Web of Science ®Google Scholar
• Isoda K, Matsuki T, Kondo H, et al. Deficiency of interleukin-1 receptor antagonist induces aortic valve disease in BALB/c mice. Arterioscler Thromb Vasc Biol. 2010;30:708–715.
   PubMed Web of Science ®Google Scholar
• Ghosh S, Hoenerhoff MJ, Clayton N, et al. Left-sided cardiac valvulitis in tristetraprolin-deficient mice: the role of tumor necrosis factor alpha. Am J Pathol. 2010;176:1484–1493.
   PubMed Web of Science ®Google Scholar
• Guo X, Yin H, Li L, et al. Cardioprotective role of tumor necrosis factor receptor-associated factor 2 by suppressing apoptosis and necroptosis. Circulation. 2017;136:729–742.
   PubMed Web of Science ®Google Scholar
• Higuchi Y, McTiernan CF, Frye CB, et al. Tumor necrosis factor receptors 1 and 2 differentially regulate survival, cardiac dysfunction, and remodeling in transgenic mice with tumor necrosis factor-alpha-induced cardiomyopathy. Circulation. 2004;109:1892–1897.
   PubMed Web of Science ®Google Scholar
• Kishore R, Tkebuchava T, Sasi SP, et al. Tumor necrosis factor-alpha signaling via TNFR1/p55 is deleterious whereas TNFR2/p75 signaling is protective in adult infarct myocardium. Adv Exp Med Biol. 2011;691:433–448.
   PubMed Web of Science ®Google Scholar
• Monden Y, Kubota T, Inoue T, et al. Tumor necrosis factor-alpha is toxic via receptor 1 and protective via receptor 2 in a murine model of myocardial infarction. Am J Physiol Heart Circ Physiol. 2007;293:H743–53.
   PubMed Web of Science ®Google Scholar
• Chan FK, Chun HJ, Zheng L, et al. A domain in TNF receptors that mediates ligand-independent receptor assembly and signaling. Science. 2000;288:2351–2354.
   PubMed Web of Science ®Google Scholar
• Naismith JH, Devine TQ, Brandhuber BJ, et al. Crystallographic evidence for dimerization of unliganded tumor necrosis factor receptor. J Biol Chem. 1995;270:13303–13307.
   PubMed Web of Science ®Google Scholar
• Moosmayer D, Wajant H, Gerlach E, et al. Characterization of different soluble TNF receptor (TNFR80) derivatives: positive influence of the intracellular domain on receptor/ligand interaction and TNF neutralization capacity. J Interferon Cytokine Res. 1996;16:471–477.
   PubMed Web of Science ®Google Scholar
• Cao J, Meng F, Gao X, et al. Expression and purification of a natural N-terminal pre-ligand assembly domain of tumor necrosis factor receptor 1 (TNFR1 PLAD) and preliminary activity determination. Protein J. 2011;30:281–289.
   PubMed Web of Science ®Google Scholar
• Mukai Y, Nakamura T, Yoshikawa M, et al. Solution of the structure of the TNF-TNFR2 complex. Sci Signal. 2010;3:ra83.
   PubMed Web of Science ®Google Scholar
• Grell M, Douni E, Wajant H, et al. The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor. Cell. 1995;83:793–802.
   PubMed Web of Science ®Google Scholar
• Schneider P, Holler N, Bodmer JL, et al. Conversion of membrane-bound Fas(CD95) ligand to its soluble form is associated with downregulation of its proapoptotic activity and loss of liver toxicity. J Exp Med. 1998;187:1205–1213.
   PubMed Web of Science ®Google Scholar
• Rauert H, Wicovsky A, Muller N, et al. Membrane tumor necrosis factor (TNF) induces p100 processing via TNF receptor-2 (TNFR2). J Biol Chem. 2010;285:7394–7404.
   PubMed Web of Science ®Google Scholar
• Wajant H. Principles of antibody-mediated TNF receptor activation. Cell Death Differ. 2015;22:1727–1741.
   PubMed Web of Science ®Google Scholar
• Park YC, Burkitt V, Villa AR, et al. Structural basis for self-association and receptor recognition of human TRAF2. Nature. 1999;398:533–538.
   PubMed Web of Science ®Google Scholar
• Mace PD, Smits C, Vaux DL, et al. Asymmetric recruitment of cIAPs by TRAF2. J Mol Biol. 2010;400:8–15.
   PubMed Web of Science ®Google Scholar
• Gerspach J, Muller D, Munkel S, et al. Restoration of membrane TNF-like activity by cell surface targeting and matrix metalloproteinase-mediated processing of a TNF prodrug. Cell Death Differ. 2006;13:273–284.
   PubMed Web of Science ®Google Scholar
• Medler J, Nelke J, Weisenberger D, et al. A general method to construct anti-TNFRSF receptor antibody fusion proteins with targeting controlled FcGR-independent agonistic activity. Cell Death Dis. 2019;10(3):224.
   PubMed Web of Science ®Google Scholar
• Sondermann P, Szymkowski DE. Harnessing Fc receptor biology in the design of therapeutic antibodies. Curr Opin Immunol. 2016;40:78–87.
   PubMed Web of Science ®Google Scholar
• Torrey H, Butterworth J, Mera T, et al. Targeting TNFR2 with antagonistic antibodies inhibits proliferation of ovarian cancer cells and tumor-associated Tregs. Sci Signal. 2017;10.
   PubMed Web of Science ®Google Scholar
• Faustman DL Antagonistic anti-tumor necrosis factor receptor superfamily antibodies. WO2016187068 2016.
   Google Scholar
• Hunig T. The rise and fall of the CD28 superagonist TGN1412 and its return as TAB08: a personal account. Febs j. 2016;283:3325–3334.
   PubMed Web of Science ®Google Scholar
• Shimizu J, Yamazaki S, Takahashi T, et al. Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat Immunol. 2002;3:135–142.
   PubMed Web of Science ®Google Scholar
• Ko K, Yamazaki S, Nakamura K, et al. Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells. J Exp Med. 2005;202:885–891.
   PubMed Web of Science ®Google Scholar
• Nishioka T, Nishida E, Iida R, et al. In vivo expansion of CD4+Foxp3+ regulatory T cells mediated by GITR molecules. Immunol Lett. 2008;121:97–104.
   PubMed Web of Science ®Google Scholar
• Kim YH, Shin SM, Choi BK, et al. Authentic GITR signaling fails to induce tumor regression unless Foxp3+ regulatory T cells are depleted. J Immunol. 2015;195:4721–4729.
   PubMed Web of Science ®Google Scholar
• Hamano R, Huang J, Yoshimura T, et al. TNF optimally activatives regulatory T cells by inducing TNF receptor superfamily members TNFR2, 4-1BB and OX40. Eur J Immunol. 2011;41:2010–2020.
   PubMed Web of Science ®Google Scholar
• Voo KS, Bover L, Harline ML, et al. Antibodies targeting human OX40 expand effector T cells and block inducible and natural regulatory T cell function. J Immunol. 2013;191:3641–3650.
   PubMed Web of Science ®Google Scholar
• Ruby CE, Yates MA, Hirschhorn-Cymerman D, et al. Cutting edge: OX40 agonists can drive regulatory T cell expansion if the cytokine milieu is right. J Immunol. 2009;183:4853–4857.
   PubMed Web of Science ®Google Scholar
• Hirschhorn-Cymerman D, Rizzuto GA, Merghoub T, et al. OX40 engagement and chemotherapy combination provides potent antitumor immunity with concomitant regulatory T cell apoptosis. J Exp Med. 2009;206:1103–1116.
   PubMed Web of Science ®Google Scholar
• Piconese S, Valzasina B, Colombo MP. OX40 triggering blocks suppression by regulatory T cells and facilitates tumor rejection. J Exp Med. 2008;205:825–839.
   PubMed Web of Science ®Google Scholar
• Piconese S, Pittoni P, Burocchi A, et al. A non-redundant role for OX40 in the competitive fitness of Treg in response to IL-2. Eur J Immunol. 2010;40:2902–2913.
   PubMed Web of Science ®Google Scholar
• Zhang P, Gao F, Wang Q, et al. Agonistic anti-4-1BB antibody promotes the expansion of natural regulatory T cells while maintaining Foxp3 expression. Scand J Immunol. 2007;66:435–440.
   PubMed Web of Science ®Google Scholar
• Akhmetzyanova I, Zelinskyy G, Littwitz-Salomon E, et al. CD137 agonist therapy can reprogram regulatory T cells into cytotoxic CD4+ T cells with antitumor activity. J Immunol. 2016;196:484–492.
   PubMed Web of Science ®Google Scholar
• Goldstein MJ, Kohrt HE, Houot R, et al. Adoptive cell therapy for lymphoma with CD4 T cells depleted of CD137-expressing regulatory T cells. Cancer Res. 2012;72:1239–1247.
   PubMed Web of Science ®Google Scholar
• Morris GP, Chen L, Kong YC. CD137 signaling interferes with activation and function of CD4+CD25+ regulatory T cells in induced tolerance to experimental autoimmune thyroiditis. Cell Immunol. 2003;226:20–29.
   PubMed Web of Science ®Google Scholar
• Claus C, Riether C, Schurch C, et al. CD27 signaling increases the frequency of regulatory T cells and promotes tumor growth. Cancer Res. 2012;72:3664–3676.
   PubMed Web of Science ®Google Scholar
• Winkels H, Meiler S, Lievens D, et al. CD27 co-stimulation increases the abundance of regulatory T cells and reduces atherosclerosis in hyperlipidaemic mice. Eur Heart J. 2017;38:3590–3599.
   PubMed Web of Science ®Google Scholar
• Mahmud SA, Manlove LS, Schmitz HM, et al. Costimulation via the tumor-necrosis factor receptor superfamily couples TCR signal strength to the thymic differentiation of regulatory T cells. Nat Immunol. 2014;15:473–481.
   PubMed Web of Science ®Google Scholar
• Coe D, Begom S, Addey C, et al. Depletion of regulatory T cells by anti-GITR mAb as a novel mechanism for cancer immunotherapy. Cancer Immunol Immunother. 2010;59:1367–1377.
   PubMed Web of Science ®Google Scholar
• Bulliard Y, Jolicoeur R, Zhang J, et al. OX40 engagement depletes intratumoral Tregs via activating FcgammaRs, leading to antitumor efficacy. Immunol Cell Biol. 2014;92:475–480.
   PubMed Web of Science ®Google Scholar
• Buchan SL, Dou L, Remer M, et al. Antibodies to costimulatory receptor 4-1BB enhance anti-tumor immunity via T regulatory cell depletion and promotion of CD8 T cell effector function. Immunity. 2018;49:958–70.e7.
   PubMed Web of Science ®Google Scholar
• Wasiuk A, Testa J, Weidlick J, et al. CD27-mediated regulatory T cell depletion and effector T cell costimulation both contribute to antitumor efficacy. J Immunol. 2017;199:4110–4123.
   PubMed Web of Science ®Google Scholar
• Loetscher H, Stueber D, Banner D, et al. Human tumor necrosis factor alpha (TNF alpha) mutants with exclusive specificity for the 55-kDa or 75-kDa TNF receptors. J Biol Chem. 1993;268:26350–26357.
   PubMed Web of Science ®Google Scholar
• Chopra M, Biehl M, Steinfatt T, et al. Exogenous TNFR2 activation protects from acute GvHD via host T reg cell expansion. J Exp Med. 2016;213:1881–1900.
   PubMed Web of Science ®Google Scholar
• Lamontain V, Schmid T, Weber-Steffens D, et al. Stimulation of TNF receptor type 2 expands regulatory T cells and ameliorates established collagen-induced arthritis in mice. Cell Mol Immunol. 2019;16(1):65–74.
   PubMed Web of Science ®Google Scholar
• Fischer R, Marsal J, Gutta C, et al. Novel strategies to mimic transmembrane tumor necrosis factor-dependent activation of tumor necrosis factor receptor 2. Sci Rep. 2017;7:6607.
   PubMed Web of Science ®Google Scholar
• Fischer R, Proske M, Duffey M, et al. Selective activation of tumor necrosis factor receptor II induces antiinflammatory responses and alleviates experimental arthritis. Arthritis Rheumatol. 2018;70:722–735.
   PubMed Web of Science ®Google Scholar
• Li F, Ravetch JV. Inhibitory Fcgamma receptor engagement drives adjuvant and anti-tumor activities of agonistic CD40 antibodies. Science. 2011;333:1030–1034.
   PubMed Web of Science ®Google Scholar
• Li F, Ravetch JV. Apoptotic and antitumor activity of death receptor antibodies require inhibitory Fcgamma receptor engagement. Proc Natl Acad Sci U S A. 2012;109:10966–10971.
   PubMed Web of Science ®Google Scholar
• Li F, Ravetch JV. Antitumor activities of agonistic anti-TNFR antibodies require differential FcgammaRIIB coengagement in vivo. Proc Natl Acad Sci U S A. 2013;110:19501–19506.
   PubMed Web of Science ®Google Scholar
• Wilson NS, Yang B, Yang A, et al. An Fcgamma receptor-dependent mechanism drives antibody-mediated target-receptor signaling in cancer cells. Cancer Cell. 2011;19:101–113.
   PubMed Web of Science ®Google Scholar
• Dahan R, Barnhart BC, Li F, et al. Therapeutic activity of agonistic, human anti-CD40 monoclonal antibodies requires selective FcgammaR engagement. Cancer Cell. 2016;29:820–831.
   PubMed Web of Science ®Google Scholar
• He LZ, Prostak N, Thomas LJ, et al. Agonist anti-human CD27 monoclonal antibody induces T cell activation and tumor immunity in human CD27-transgenic mice. J Immunol. 2013;191:4174–4183.
   PubMed Web of Science ®Google Scholar
• Zhang D, Goldberg MV, Chiu ML. Fc engineering approaches to enhance the agonism and effector functions of an Anti-OX40 antibody. J Biol Chem. 2016;291:27134–27146.
   PubMed Web of Science ®Google Scholar
• Salzmann S, Seher A, Trebing J, et al. Fibroblast growth factor inducible (Fn14)-specific antibodies concomitantly display signaling pathway-specific agonistic and antagonistic activity. J Biol Chem. 2013;288:13455–13466.
   PubMed Web of Science ®Google Scholar
• Steed PM, Tansey MG, Zalevsky J, et al. Inactivation of TNF signaling by rationally designed dominant-negative TNF variants. Science. 2003;301:1895–1898.
   PubMed Web of Science ®Google Scholar
• Zalevsky J, Secher T, Ezhevsky SA, et al. Dominant-negative inhibitors of soluble TNF attenuate experimental arthritis without suppressing innate immunity to infection. J Immunol. 2007;179:1872–1883.
   PubMed Web of Science ®Google Scholar
• Maillet I, Schnyder-Candrian S, Couillin I, et al. Allergic lung inflammation is mediated by soluble tumor necrosis factor (TNF) and attenuated by dominant-negative TNF biologics. Am J Respir Cell Mol Biol. 2011;45:731–739.
   PubMed Web of Science ®Google Scholar
• Olleros ML, Vesin D, Lambou AF, et al. Dominant-negative tumor necrosis factor protects from Mycobacterium bovis Bacillus Calmette Guerin (BCG) and endotoxin-induced liver injury without compromising host immunity to BCG and Mycobacterium tuberculosis. J Infect Dis. 2009;199:1053–1063.
   PubMed Web of Science ®Google Scholar