Constitutively active GSK3β as a means to bolster dendritic cell functionality in the face of tumour-mediated immune suppression

References

• Steinman RM. Lasker basic medical research award. Dendritic cells: versatile controllers of the immune system. Nat Med. 2007;13:1155–1159. doi:10.1038/nm1643.
   PubMed Web of Science ®Google Scholar
• Hangalapura BN, Timares L, Oosterhoff D, Scheper RJ, Curiel DT, de Gruijl TD. CD40-targeted adenoviral cancer vaccines: the long and winding road to the clinic. J Gene Med. 2012;14:416–427. doi:10.1002/jgm.1648.
   PubMed Web of Science ®Google Scholar
• Kreutz M, Tacken PJ, Figdor CG. Targeting dendritic cells–why bother? Blood. 2013;121:2836–2844. doi:10.1182/blood-2012-09-452078.
   PubMed Web of Science ®Google Scholar
• Steinman RM. Decisions about dendritic cells: past, present, and future. Annu Rev Immunol. 2012;30:1–22. doi:10.1146/annurev-immunol-100311-102839.
   PubMed Web of Science ®Google Scholar
• Spranger S, Bao R, Gajewski TF. Melanoma-intrinsic beta-catenin signalling prevents anti-tumour immunity. Nature. 2015;523:231–235. doi:10.1038/nature14404.
   PubMed Web of Science ®Google Scholar
• Spranger S, Dai D, Horton B, Gajewski TF. Tumor-residing batf3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy. Cancer Cell. 2017;31:711–723 e714. doi:10.1016/j.ccell.2017.04.003.
   PubMed Web of Science ®Google Scholar
• Ribas A, Dummer R, Puzanov I, VanderWalde A, Andtbacka RHI, Michielin O, Olszanski AJ, Malvehy J, Cebon J, Fernandez E, et al. Oncolytic virotherapy promotes intratumoral T cell infiltration and improves anti-PD-1 immunotherapy. Cell. 2017;170:1109–1119 e1110. doi:10.1016/j.cell.2017.08.027.
   PubMed Web of Science ®Google Scholar
• Tivnan A, Heilinger T, Lavelle EC, Prehn JH. Advances in immunotherapy for the treatment of glioblastoma. J Neurooncol. 2017;131:1–9. doi:10.1007/s11060-016-2299-2.
   PubMed Web of Science ®Google Scholar
• Ben-Neriah Y, Karin M. Inflammation meets cancer, with NF-kappaB as the matchmaker. Nat Immunol. 2011;12:715–723. doi:10.1038/ni.2060.
   PubMed Web of Science ®Google Scholar
• Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454:436–444. doi:10.1038/nature07205.
   PubMed Web of Science ®Google Scholar
• Mantovani A, Allavena P, Sozzani S, Vecchi A, Locati M, Sica A. Chemokines in the recruitment and shaping of the leukocyte infiltrate of tumors. Semin Cancer Biol. 2004;14:155–160. doi:10.1016/j.semcancer.2003.10.001.
   PubMed Web of Science ®Google Scholar
• Zou W. Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer. 2005;5:263–274. doi:10.1038/nrc1586.
   PubMed Web of Science ®Google Scholar
• Qin A, Coffey DG, Warren EH, Ramnath N. Mechanisms of immune evasion and current status of checkpoint inhibitors in non-small cell lung cancer. Cancer Med. 2016;5:2567–2578. doi:10.1002/cam4.819.
   PubMed Web of Science ®Google Scholar
• Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer. 2004;4:71–78. doi:10.1038/nrc1256.
   PubMed Web of Science ®Google Scholar
• Allavena P, Piemonti L, Longoni D, Bernasconi S, Stoppacciaro A, Ruco L, Mantovani A. IL-10 prevents the differentiation of monocytes to dendritic cells but promotes their maturation to macrophages. Eur J Immunol. 1998;28:359–369. doi:10.1002/(SICI)1521-4141(199801)28:01<359::AID-IMMU359>3.0.CO;2-4.
   PubMed Web of Science ®Google Scholar
• De Smedt T, Van Mechelen M, De Becker G, Urbain J, Leo O, Moser M. Effect of interleukin-10 on dendritic cell maturation and function. Eur J Immunol. 1997;27:1229–1235. doi:10.1002/eji.1830270526.
   PubMed Web of Science ®Google Scholar
• Enk AH, Angeloni VL, Udey MC, Katz SI. Inhibition of Langerhans cell antigen-presenting function by IL-10. A role for IL-10 in induction of tolerance. J Immunol. 1993;151:2390–2398.
   PubMed Web of Science ®Google Scholar
• Steinbrink K, Wolfl M, Jonuleit H, Knop J, Enk AH. Induction of tolerance by IL-10-treated dendritic cells. J Immunol. 1997;159:4772–4780.
   PubMed Web of Science ®Google Scholar
• Allavena P, Piemonti L, Longoni D, Bernasconi S, Stoppacciaro A, Ruco L, Mantovani A. IL-10 prevents the generation of dendritic cells from CD14+ blood monocytes, promotes the differentiation to mature macrophages and stimulates endocytosis of FITC-dextran. Adv Exp Med Biol. 1997;417:323–327.
   PubMed Web of Science ®Google Scholar
• Buelens C, Verhasselt V, De Groote D, Thielemans K, Goldman M, Willems F. Interleukin-10 prevents the generation of dendritic cells from human peripheral blood mononuclear cells cultured with interleukin-4 and granulocyte/macrophage-colony-stimulating factor. Eur J Immunol. 1997;27:756–762. doi:10.1002/eji.1830270326.
   PubMed Web of Science ®Google Scholar
• Lindenberg JJ, van de Ven R, Lougheed SM, Zomer A, Santegoets SJ, Griffioen AW, Hooijberg E, van Den Eertwegh AJ, Thijssen VL, Scheper RJ, et al. Functional characterization of a STAT3-dependent dendritic cell-derived CD14(+) cell population arising upon IL-10-driven maturation. Oncoimmunology. 2013;2:e23837. doi:10.4161/onci.23837.
   PubMed Web of Science ®Google Scholar
• de Gruijl TD, Sombroek CC, Lougheed SM, Oosterhoff D, Buter J, van Den Eertwegh AJ, Scheper RJ, Pinedo HM. A postmigrational switch among skin-derived dendritic cells to a macrophage-like phenotype is predetermined by the intracutaneous cytokine balance. J Immunol. 2006;176:7232–7242. doi:10.4049/jimmunol.176.12.7232.
   PubMed Web of Science ®Google Scholar
• Lindenberg JJ, Oosterhoff D, Sombroek CC, Lougheed SM, Hooijberg E, Stam AG, Santegoets SJ, Tijssen HJ, Buter J, Pinedo HM, et al. IL-10 conditioning of human skin affects the distribution of migratory dendritic cell subsets and functional T cell differentiation. PLoS One. 2013;8:e70237. doi:10.1371/journal.pone.0070237.
   PubMed Web of Science ®Google Scholar
• Sombroek CC, Stam AG, Masterson AJ, Lougheed SM, Schakel MJ, Meijer CJ, Pinedo HM, van Den Eertwegh AJ, Scheper RJ, de Gruijl TD. Prostanoids play a major role in the primary tumor-induced inhibition of dendritic cell differentiation. J Immunol. 2002;168:4333–4343. doi:10.4049/jimmunol.168.9.4333.
   PubMed Web of Science ®Google Scholar
• Nefedova Y, Cheng P, Gilkes D, Blaskovich M, Beg AA, Sebti SM, Gabrilovich DI. Activation of dendritic cells via inhibition of Jak2/STAT3 signaling. J Immunol. 2005;175:4338–4346. doi:10.4049/jimmunol.175.7.4338.
   PubMed Web of Science ®Google Scholar
• Wang T, Niu G, Kortylewski M, Burdelya L, Shain K, Zhang S, Bhattacharya R, Gabrilovich D, Heller R, Coppola D, et al. Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells. Nat Med. 2004;10:48–54. doi:10.1038/nm976.
   PubMed Web of Science ®Google Scholar
• Yu H, Kortylewski M, Pardoll D. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol. 2007;7:41–51. doi:10.1038/nri1995.
   PubMed Web of Science ®Google Scholar
• Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer. 2009;9:798–809. doi:10.1038/nrc2734.
   PubMed Web of Science ®Google Scholar
• Masterson AJ, Sombroek CC, De Gruijl TD, Graus YM, van der Vliet HJ, Lougheed SM, van Den Eertwegh AJ, Pinedo HM, Scheper RJ. MUTZ-3, a human cell line model for the cytokine-induced differentiation of dendritic cells from CD34+ precursors. Blood. 2002;100:701–703. doi:10.1182/blood.v100.2.701.
   PubMed Web of Science ®Google Scholar
• Santegoets SJ, van Den Eertwegh AJ, van de Loosdrecht AA, Scheper RJ, de Gruijl TD. Human dendritic cell line models for DC differentiation and clinical DC vaccination studies. J Leukoc Biol. 2008;84:1364–1373. doi:10.1189/jlb.0208092.
   PubMed Web of Science ®Google Scholar
• Oosterhoff D, Lougheed S, van de Ven R, Lindenberg J, van Cruijsen H, Hiddingh L, Kroon J, van Den Eertwegh AJ, Hangalapura B, Scheper RJ, et al. Tumor-mediated inhibition of human dendritic cell differentiation and function is consistently counteracted by combined p38 MAPK and STAT3 inhibition. Oncoimmunology. 2012;1:649–658. doi:10.4161/onci.20365.
   PubMed Web of Science ®Google Scholar
• Tan YF, Leong CF, Cheong SK. Observation of dendritic cell morphology under light, phase-contrast or confocal laser scanning microscopy. Malays J Pathol. 2010;32:97–102.
   PubMedGoogle Scholar
• Rodionova E, Conzelmann M, Maraskovsky E, Hess M, Kirsch M, Giese T, Ho AD, Zoller M, Dreger P, Luft T. GSK-3 mediates differentiation and activation of proinflammatory dendritic cells. Blood. 2007;109:1584–1592. doi:10.1182/blood-2006-06-028951.
   PubMed Web of Science ®Google Scholar
• Maixner DW, Weng HR. The role of glycogen synthase kinase 3 beta in neuroinflammation and pain. J Pharm Pharmacol. 2013;1:001. doi:10.13188/2327-204X.1000001.
   Google Scholar
• van Cruijsen H, Oosterhoff D, Lindenberg JJ, Lougheed SM, Fehres C, Weijers K, van Boerdonk R, Giaccone G, Scheper RJ, Hoekman K, et al. Glioblastoma-induced inhibition of Langerhans cell differentiation from CD34(+) precursors is mediated by IL-6 but unaffected by JAK2/STAT3 inhibition. Immunotherapy. 2011;3:1051–1061. doi:10.2217/imt.11.107.
   PubMed Web of Science ®Google Scholar
• van Baal JW, Diks SH, Wanders RJ, Rygiel AM, Milano F, Joore J, Bergman JJ, Peppelenbosch MP, Krishnadath KK. Comparison of kinome profiles of Barrett’s esophagus with normal squamous esophagus and normal gastric cardia. Cancer Res. 2006;66:11605–11612. doi:10.1158/0008-5472.CAN-06-1370.
   PubMed Web of Science ®Google Scholar
• Azijli K, Yuvaraj S, Peppelenbosch MP, Wurdinger T, Dekker H, Joore J, van Dijk E, Quax WJ, Peters GJ, de Jong S, et al. Kinome profiling of non-canonical TRAIL signaling reveals RIP1-Src-STAT3-dependent invasion in resistant non-small cell lung cancer cells. J Cell Sci. 2012;125:4651–4661. doi:10.1242/jcs.109587.
   PubMed Web of Science ®Google Scholar
• Swafford D, Manicassamy S. Wnt signaling in dendritic cells: its role in regulation of immunity and tolerance. Discov Med. 2015;19:303–310.
   PubMed Web of Science ®Google Scholar
• Tapia JC, Torres VA, Rodriguez DA, Leyton L, Quest AF. Casein kinase 2 (CK2) increases survivin expression via enhanced beta-catenin-T cell factor/lymphoid enhancer binding factor-dependent transcription. Proc Natl Acad Sci U S A. 2006;103:15079–15084. doi:10.1073/pnas.0606845103.
   PubMed Web of Science ®Google Scholar
• Soriano S, Kang DE, Fu M, Pestell R, Chevallier N, Zheng H, Koo EH. Presenilin 1 negatively regulates beta-catenin/T cell factor/lymphoid enhancer factor-1 signaling independently of beta-amyloid precursor protein and notch processing. J Cell Biol. 2001;152:785–794. doi:10.1083/jcb.152.4.785.
   PubMed Web of Science ®Google Scholar
• Xia X, Qian S, Soriano S, Wu Y, Fletcher AM, Wang XJ, Koo EH, Wu X, Zheng H. Loss of presenilin 1 is associated with enhanced beta-catenin signaling and skin tumorigenesis. Proc Natl Acad Sci U S A. 2001;98:10863–10868. doi:10.1073/pnas.191284198.
   PubMed Web of Science ®Google Scholar
• Cortes-Vieyra R, Bravo-Patino A, Valdez-Alarcon JJ, Juarez MC, Finlay BB, Baizabal-Aguirre VM. Role of glycogen synthase kinase-3 beta in the inflammatory response caused by bacterial pathogens. J Inflamm (Lond). 2012;9:23. doi:10.1186/1476-9255-9-23.
   PubMed Web of Science ®Google Scholar
• Wang H, Brown J, Garcia CA, Tang Y, Benakanakere MR, Greenway T, Alard P, Kinane DF, Martin M. The role of glycogen synthase kinase 3 in regulating IFN-beta-mediated IL-10 production. J Immunol. 2011;186:675–684. doi:10.4049/jimmunol.1001473.
   PubMed Web of Science ®Google Scholar
• Alessandrini A, De Haseth S, Fray M, Miyajima M, Colvin RB, Williams WW, Benedict Cosimi A, Benichou G. Dendritic cell maturation occurs through the inhibition of GSK-3beta. Cell Immunol. 2011;270:114–125. doi:10.1016/j.cellimm.2011.04.007.
   PubMed Web of Science ®Google Scholar
• Zhou J, Cheng P, Youn JI, Cotter MJ, Gabrilovich DI. Notch and wingless signaling cooperate in regulation of dendritic cell differentiation. Immunity. 2009;30:845–859. doi:10.1016/j.immuni.2009.03.021.
   PubMed Web of Science ®Google Scholar
• Manoharan I, Hong Y, Suryawanshi A, Angus-Hill ML, Sun Z, Mellor AL, Munn DH, Manicassamy S. TLR2-dependent activation of beta-catenin pathway in dendritic cells induces regulatory responses and attenuates autoimmune inflammation. J Immunol. 2014;193:4203–4213. doi:10.4049/jimmunol.1400614.
   PubMed Web of Science ®Google Scholar
• Valencia J, Hernandez-Lopez C, Martinez VG, Hidalgo L, Zapata AG, Vicente A, Varas A, Sacedon R. Wnt5a skews dendritic cell differentiation to an unconventional phenotype with tolerogenic features. J Immunol. 2011;187:4129–4139. doi:10.4049/jimmunol.1101243.
   PubMed Web of Science ®Google Scholar
• Zizzari IG, Napoletano C, Botticelli A, Caponnetto S, Calabro F, Gelibter A, Rughetti A, Ruscito I, Rahimi H, Rossi E, et al. TK inhibitor pazopanib primes DCs by downregulation of the beta-catenin pathway. Cancer Immunol Res. 2018;6:711–722. doi:10.1158/2326-6066.CIR-17-0594.
   PubMed Web of Science ®Google Scholar
• Jiang A, Bloom O, Ono S, Cui W, Unternaehrer J, Jiang S, Whitney JA, Connolly J, Banchereau J, Mellman I. Disruption of E-cadherin-mediated adhesion induces a functionally distinct pathway of dendritic cell maturation. Immunity. 2007;27:610–624. doi:10.1016/j.immuni.2007.08.015.
   PubMed Web of Science ®Google Scholar
• Wang S, Hong S, Yang J, Qian J, Zhang X, Shpall E, Kwak LW, Yi Q. Optimizing immunotherapy in multiple myeloma: restoring the function of patients’ monocyte-derived dendritic cells by inhibiting p38 or activating MEK/ERK MAPK and neutralizing interleukin-6 in progenitor cells. Blood. 2006;108:4071–4077. doi:10.1182/blood-2006-04-016980.
   PubMed Web of Science ®Google Scholar
• Xie J, Qian J, Yang J, Wang S, Freeman ME 3rd, Yi Q. Critical roles of Raf/MEK/ERK and PI3K/AKT signaling and inactivation of p38 MAP kinase in the differentiation and survival of monocyte-derived immature dendritic cells. Exp Hematol. 2005;33:564–572. doi:10.1016/j.exphem.2005.03.001.
   PubMed Web of Science ®Google Scholar
• Bikkavilli RK, Feigin ME, Malbon CC. p38 mitogen-activated protein kinase regulates canonical Wnt-beta-catenin signaling by inactivation of GSK3beta. J Cell Sci. 2008;121:3598–3607. doi:10.1242/jcs.032854.
   PubMed Web of Science ®Google Scholar
• Harizi H, Limem I, Gualde N. CD40 engagement on dendritic cells induces cyclooxygenase-2 and EP2 receptor via p38 and ERK MAPKs. Immunol Cell Biol. 2011;89:275–282. doi:10.1038/icb.2010.94.
   PubMed Web of Science ®Google Scholar
• Qian C, Qian L, Yu Y, An H, Guo Z, Han Y, Chen Y, Bai Y, Wang Q, Cao X. Fas signal promotes the immunosuppressive function of regulatory dendritic cells via the ERK/beta-catenin pathway. J Biol Chem. 2013;288:27825–27835. doi:10.1074/jbc.M112.425751.
   PubMed Web of Science ®Google Scholar
• Den Haan JM, Lehar SM, Bevan MJ. CD8(+) but not CD8(-) dendritic cells cross-prime cytotoxic T cells in vivo. J Exp Med. 2000;192:1685–1696. doi:10.1084/jem.192.12.1685.
   PubMed Web of Science ®Google Scholar
• Schulz O, Reis E Sousa C. Cross-presentation of cell-associated antigens by CD8alpha+ dendritic cells is attributable to their ability to internalize dead cells. Immunology. 2002;107:183–189. doi:10.1046/j.1365-2567.2002.01513.x.
   PubMed Web of Science ®Google Scholar
• Fujimoto K, Karuppuchamy T, Takemura N, Shimohigoshi M, Machida T, Haseda Y, Aoshi T, Ishii KJ, Akira S, Uematsu S. A new subset of CD103+CD8alpha+ dendritic cells in the small intestine expresses TLR3, TLR7, and TLR9 and induces Th1 response and CTL activity. J Immunol. 2011;186:6287–6295. doi:10.4049/jimmunol.1004036.
   PubMed Web of Science ®Google Scholar
• Preynat-Seauve O, Schuler P, Contassot E, Beermann F, Huard B, French LE. Tumor-infiltrating dendritic cells are potent antigen-presenting cells able to activate T cells and mediate tumor rejection. J Immunol. 2006;176:61–67. doi:10.4049/jimmunol.176.1.61.
   PubMed Web of Science ®Google Scholar
• Dunne PJ, Moran B, Cummins RC, Mills KH. CD11c+CD8alpha+ dendritic cells promote protective immunity to respiratory infection with bordetella pertussis. J Immunol. 2009;183:400–410. doi:10.4049/jimmunol.0900169.
   PubMed Web of Science ®Google Scholar
• Parikh K, Diks SH, Tuynman JH, Verhaar A, Lowenberg M, Hommes DW, Joore J, Pandey A, Peppelenbosch MP. Comparison of peptide array substrate phosphorylation of c-Raf and mitogen activated protein kinase kinase kinase 8. PLoS One. 2009;4:e6440. doi:10.1371/journal.pone.0006440.
   PubMed Web of Science ®Google Scholar
• Santegoets SJ, Masterson AJ, van der Sluis PC, Lougheed SM, Fluitsma DM, van Den Eertwegh AJ, Pinedo HM, Scheper RJ, de Gruijl TD. A CD34(+) human cell line model of myeloid dendritic cell differentiation: evidence for a CD14(+)CD11b(+) Langerhans cell precursor. J Leukoc Biol. 2006;80:1337–1344. doi:10.1189/jlb.0206111.
   PubMed Web of Science ®Google Scholar
• Johnson JP, Demmer-Dieckmann M, Meo T, Hadam MR, Riethmuller G. Surface antigens of human melanoma cells defined by monoclonal antibodies. I. Biochemical characterization of two antigens found on cell lines and fresh tumors of diverse tissue origin. Eur J Immunol. 1981;11:825–831. doi:10.1002/eji.1830111015.
   PubMed Web of Science ®Google Scholar
• Park KW, Yang HM, Youn SW, Yang HJ, Chae IH, Oh BH, Lee MM, Park YB, Choi YS, Kim HS, et al. Constitutively active glycogen synthase kinase-3beta gene transfer sustains apoptosis, inhibits proliferation of vascular smooth muscle cells, and reduces neointima formation after balloon injury in rats. Arterioscler Thromb Vasc Biol. 2003;23:1364–1369. doi:10.1161/01.ATV.0000081633.53390.B4.
   PubMed Web of Science ®Google Scholar