Up-regulation of Core 1 Beta 1, 3-Galactosyltransferase Suppresses Osteosarcoma Growth with Induction of IFN-γ Secretion and Proliferation of CD8+ T Cells

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Abstract

Aim: Abnormal glycosylation often occurs in tumor cells. T-synthase (core 1 beta 1,3- galactosyltransferase, C1GALT1, or T-synthase) is a key enzyme involved in O-glycosylation. Although T-synthase is known to be important in human tumors, the effects of T-synthase and T-antigen on human tumor responses remain poorly defined.

Methods: In this study, a T-synthase-specific short hairpin RNA (shRNA) or T-synthase-specific eukaryotic expression vector(pcDNA3.1(+)) was transfected into murine Osteosarcoma LM8 cells to assess the effects of T-synthase on T cells and cytokines.

Results: The up-regulation of T-synthase promoted the proliferation of osteosarcoma cells in vitro, but it promoted the proliferation of tumor initially up to 2-3 weeks but showed significant growth inhibitory effect after 3 weeks post-implantation in vivo. Osteosarcoma cells with high T-synthase expression in vitro promoted the proliferation and inhibited the apoptosis of CD8+ T cells. Further, T-synthase upregulation promoted CD8+ T-cell proliferation and the increased production of CD4+ T cell-derived IFN-γ cytokines to induce the increased tumor lethality of CTLs.

Conclusion: Our data suggest that high T-synthase expression inhibits tumor growth by improving the body's anti-tumor immunity. Therefore, using this characteristic to prepare tumor cell vaccines with high immunogenicity provides a new idea for clinical immunotherapy of osteosarcoma.

Graphical Abstract

Animated Abstract

[1]
Wedekind, M.F.; Wagner, L.M.; Cripe, T.P. Immunotherapy for osteosarcoma: Where do we go from here? Pediatr. Blood Cancer, 2018, 65(9), e27227.
[http://dx.doi.org/10.1002/pbc.27227] [PMID: 29923370]
[2]
Rickel, K.; Fang, F.; Tao, J. Molecular genetics of osteosarcoma. Bone, 2017, 102, 69-79.
[http://dx.doi.org/10.1016/j.bone.2016.10.017] [PMID: 27760307]
[3]
Casali, P.G.; Bielack, S.; Abecassis, N.; Aro, H.T.; Bauer, S.; Biagini, R.; Bonvalot, S.; Boukovinas, I.; Bovee, J.V.M.G.; Brennan, B.; Brodowicz, T.; Broto, J.M.; Brugières, L.; Buonadonna, A.; De Álava, E.; Dei Tos, A.P.; Del Muro, X.G.; Dileo, P.; Dhooge, C.; Eriksson, M.; Fagioli, F.; Fedenko, A.; Ferraresi, V.; Ferrari, A.; Ferrari, S.; Frezza, A.M.; Gaspar, N.; Gasperoni, S.; Gelderblom, H.; Gil, T.; Grignani, G.; Gronchi, A.; Haas, R.L.; Hassan, B.; Hecker-Nolting, S.; Hohenberger, P.; Issels, R.; Joensuu, H.; Jones, R.L.; Judson, I.; Jutte, P.; Kaal, S.; Kager, L.; Kasper, B.; Kopeckova, K.; Krákorová, D.A.; Ladenstein, R.; Le Cesne, A.; Lugowska, I.; Merimsky, O.; Montemurro, M.; Morland, B.; Pantaleo, M.A.; Piana, R.; Picci, P.; Piperno-Neumann, S.; Pousa, A.L.; Reichardt, P.; Robinson, M.H.; Rutkowski, P.; Safwat, A.A.; Schöffski, P.; Sleijfer, S.; Stacchiotti, S.; Strauss, S.J.; Sundby Hall, K.; Unk, M.; Van Coevorden, F.; van der Graaf, W.T.A.; Whelan, J.; Wardelmann, E.; Zaikova, O.; Blay, J.Y. Bone sarcomas: ESMO–PaedCan–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol., 2018, 29(Suppl. 4), 79-95.
[http://dx.doi.org/10.1093/annonc/mdy310] [PMID: 30285218]
[4]
Ługowska, I.; Pieńkowski, A.; Szumera-Ciećkiewicz, A.; Koseła- Paterczyk, H.; Teterycz, P.; Głogowski, M. The long-term treatment outcomes of adult osteosarcoma. Pol. Merkuriusz Lek., 2017, 42, 158-164.
[5]
Harrison, D.J.; Geller, D.S.; Gill, J.D.; Lewis, V.O.; Gorlick, R. Current and future therapeutic approaches for osteosarcoma. Expert Rev. Anticancer Ther., 2018, 18(1), 39-50.
[http://dx.doi.org/10.1080/14737140.2018.1413939] [PMID: 29210294]
[6]
Roberts, R.D.; Lizardo, M.M.; Reed, D.R.; Hingorani, P.; Glover, J.; Allen-Rhoades, W.; Fan, T.; Khanna, C.; Sweet-Cordero, E.A.; Cash, T.; Bishop, M.W.; Hegde, M.; Sertil, A.R.; Koelsche, C.; Mirabello, L.; Malkin, D.; Sorensen, P.H.; Meltzer, P.S.; Janeway, K.A.; Gorlick, R.; Crompton, B.D. Provocative questions in osteosarcoma basic and translational biology: A report from the Children’s Oncology Group. Cancer, 2019, 125(20), 3514-3525.
[http://dx.doi.org/10.1002/cncr.32351] [PMID: 31355930]
[7]
Picci, P. Osteosarcoma (Osteogenic sarcoma). Orphanet J. Rare Dis., 2007, 2(1), 6.
[http://dx.doi.org/10.1186/1750-1172-2-6] [PMID: 17244349]
[8]
Zhang, Y.; Yang, J.; Zhao, N.; Wang, C.; Kamar, S.; Zhou, Y.; He, Z.; Yang, J.; Sun, B.; Shi, X.; Han, L.; Yang, Z. Progress in the chemotherapeutic treatment of osteosarcoma. (Review) Oncol. Lett., 2018, 16(5), 6228-6237.
[http://dx.doi.org/10.3892/ol.2018.9434] [PMID: 30405759]
[9]
Bousquet, M.; Noirot, C.; Accadbled, F.; Sales de Gauzy, J.; Castex, M.P.; Brousset, P.; Gomez-Brouchet, A. Whole-exome sequencing in osteosarcoma reveals important heterogeneity of genetic alterations. Ann. Oncol., 2016, 27(4), 738-744.
[http://dx.doi.org/10.1093/annonc/mdw009] [PMID: 26787232]
[10]
Ho, X.D.; Phung, P.; Q Le, V. ; H Nguyen, V.; Reimann, E.; Prans, E.; Kõks, G.; Maasalu, K.; Le, N.T.N.; H Trinh, L.; G Nguyen, H.; Märtson, A.; Kõks, S. Whole transcriptome analysis identifies differentially regulated networks between osteosarcoma and normal bone samples. Exp. Biol. Med., 2017, 242(18), 1802-1811.
[http://dx.doi.org/10.1177/1535370217736512] [PMID: 29050494]
[11]
Lee-Sundlov, M.M.; Stowell, S.R.; Hoffmeister, K.M. Multifaceted role of glycosylation in transfusion medicine, platelets, and red blood cells. J. Thromb. Haemost., 2020, 18(7), 1535-1547.
[http://dx.doi.org/10.1111/jth.14874] [PMID: 32350996]
[12]
Munkley, J.; Elliott, D.J. Hallmarks of glycosylation in cancer. Oncotarget, 2016, 7(23), 35478-35489.
[http://dx.doi.org/10.18632/oncotarget.8155] [PMID: 27007155]
[13]
Vajaria, B.N.; Patel, P.S. Glycosylation: A hallmark of cancer? Glycoconj. J., 2017, 34(2), 147-156.
[http://dx.doi.org/10.1007/s10719-016-9755-2] [PMID: 27975160]
[14]
Shan, A.; Lu, J.; Xu, Z.; Li, X.; Xu, Y.; Li, W.; Liu, F.; Yang, F.; Sato, T.; Narimatsu, H.; Zhang, Y. Polypeptide N-acetylgalactosaminyltransferase 18 non-catalytically regulates the ER homeostasis and O-glycosylation. Biochim. Biophys. Acta, 2019, 1863(5), 870-882.
[http://dx.doi.org/10.1016/j.bbagen.2019.01.009] [PMID: 30797803]
[15]
Gupta, R.; Leon, F.; Rauth, S.; Batra, S.K.; Ponnusamy, M.P. A systematic review on the implications of O-linked glycan branching and truncating enzymes on cancer progression and metastasis. Cells, 2020, 9(2), 446.
[http://dx.doi.org/10.3390/cells9020446] [PMID: 32075174]
[16]
Lee, P.C.; Chen, S.T.; Kuo, T.C.; Lin, T.C.; Lin, M.C.; Huang, J.; Hung, J.S.; Hsu, C.L.; Juan, H.F.; Lee, P.H.; Huang, M.C. C1GALT1 is associated with poor survival and promotes soluble Ephrin A1-mediated cell migration through activation of EPHA2 in gastric cancer. Oncogene, 2020, 39(13), 2724-2740.
[http://dx.doi.org/10.1038/s41388-020-1178-7] [PMID: 32005975]
[17]
Wu, Y.M.; Liu, C.H.; Huang, M.J.; Lai, H.S.; Lee, P.H.; Hu, R.H.; Huang, M.C. C1GALT1 enhances proliferation of hepatocellular carcinoma cells via modulating MET glycosylation and dimerization. Cancer Res., 2013, 73(17), 5580-5590.
[http://dx.doi.org/10.1158/0008-5472.CAN-13-0869] [PMID: 23832667]
[18]
Ju, T.; Cummings, R.D.; Canfield, W.M. Purification, characterization, and subunit structure of rat core 1 Beta1,3-galactosyltransferase. J. Biol. Chem., 2002, 277(1), 169-177.
[http://dx.doi.org/10.1074/jbc.M109056200] [PMID: 11673471]
[19]
Fu, C.; Zhao, H.; Wang, Y.; Cai, H.; Xiao, Y.; Zeng, Y.; Chen, H. Tumor-associated antigens: Tn antigen, sTn antigen, and T antigen. HLA, 2016, 88(6), 275-286.
[http://dx.doi.org/10.1111/tan.12900] [PMID: 27679419]
[20]
Lin, M.C.; Chien, P.H.; Wu, H.Y.; Chen, S.T.; Juan, H.F.; Lou, P.J.; Huang, M.C. C1GALT1 predicts poor prognosis and is a potential therapeutic target in head and neck cancer. Oncogene, 2018, 37(43), 5780-5793.
[http://dx.doi.org/10.1038/s41388-018-0375-0] [PMID: 29930379]
[21]
Chou, C.H.; Huang, M.J.; Chen, C.H.; Shyu, M.K.; Huang, J.; Hung, J.S.; Huang, C.S.; Huang, M.C. Up-regulation of C1GALT1 promotes breast cancer cell growth through MUC1-C signaling pathway. Oncotarget, 2015, 6(8), 6123-6135.
[http://dx.doi.org/10.18632/oncotarget.3045] [PMID: 25762620]
[22]
Chen, H.D.; Zhou, X.; Yu, G.; Zhao, Y.L.; Ren, Y.; Zhou, Y.D.; Li, Q.; Zhang, X.L. Knockdown of core 1 beta 1, 3-galactosyltransferase prolongs skin allograft survival with induction of galectin-1 secretion and suppression of CD8+ T cells: T synthase knockdown effects on galectin-1 and CD8+ T cells. J. Clin. Immunol., 2012, 32(4), 820-836.
[http://dx.doi.org/10.1007/s10875-012-9653-8] [PMID: 22392045]
[23]
Mosmann, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods, 1983, 65(1-2), 55-63.
[http://dx.doi.org/10.1016/0022-1759(83)90303-4] [PMID: 6606682]
[24]
Liu, M.; Chen, H.; Luo, F.; Li, P.; Pan, Q.; Xia, B.; Qi, Z.; Ho, W.Z.; Zhang, X.L. Deletion of N-glycosylation sites of hepatitis C virus envelope protein E1 enhances specific cellular and humoral immune responses. Vaccine, 2007, 25(36), 6572-6580.
[http://dx.doi.org/10.1016/j.vaccine.2007.07.003] [PMID: 17675185]
[25]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2018. CA Cancer J. Clin., 2018, 68(1), 7-30.
[http://dx.doi.org/10.3322/caac.21442] [PMID: 29313949]
[26]
Lussier, D.M.; Johnson, J.L.; Hingorani, P.; Blattman, J.N. Combination immunotherapy with α-CTLA-4 and α-PD-L1 antibody blockade prevents immune escape and leads to complete control of metastatic osteosarcoma. J. Immunother. Cancer, 2015, 3(1), 21.
[http://dx.doi.org/10.1186/s40425-015-0067-z] [PMID: 25992292]
[27]
Mason, N.J.; Gnanandarajah, J.S.; Engiles, J.B.; Gray, F.; Laughlin, D.; Gaurnier-Hausser, A.; Wallecha, A.; Huebner, M.; Paterson, Y. Immunotherapy with a HER2-targeting Listeria Induces HER2-specific immunity and demonstrates potential therapeutic effects in a Phase I trial in canine osteosarcoma. Clin. Cancer Res., 2016, 22(17), 4380-4390.
[http://dx.doi.org/10.1158/1078-0432.CCR-16-0088] [PMID: 26994144]
[28]
Yoshida, K.; Okamoto, M.; Sasaki, J.; Kuroda, C.; Ishida, H.; Ueda, K.; Ideta, H.; Kamanaka, T.; Sobajima, A.; Takizawa, T.; Tanaka, M.; Aoki, K.; Uemura, T.; Kato, H.; Haniu, H.; Saito, N. Anti-PD-1 antibody decreases tumour-infiltrating regulatory T cells. BMC Cancer, 2020, 20(1), 25.
[http://dx.doi.org/10.1186/s12885-019-6499-y] [PMID: 31914969]
[29]
Miwa, S.; Shirai, T.; Yamamoto, N.; Hayashi, K.; Takeuchi, A.; Igarashi, K.; Tsuchiya, H. Current and emerging targets in immunotherapy for osteosarcoma. J. Oncol., 2019, 2019, 7035045.
[http://dx.doi.org/10.1155/2019/7035045] [PMID: 30693030]
[30]
Cervoni, G.E.; Cheng, J.J.; Stackhouse, K.A.; Heimburg-Molinaro, J.; Cummings, R.D. O-glycan recognition and function in mice and human cancers. Biochem. J., 2020, 477(8), 1541-1564.
[http://dx.doi.org/10.1042/BCJ20180103] [PMID: 32348475]
[31]
Sun, X.; Zhan, M.; Sun, X.; Liu, W.; Meng, X. C1GALT1 in health and disease. Oncol. Lett., 2021, 22(2), 589.
[http://dx.doi.org/10.3892/ol.2021.12850] [PMID: 34149900]
[32]
Chugh, S.; Barkeer, S.; Rachagani, S.; Nimmakayala, R.K.; Perumal, N.; Pothuraju, R.; Atri, P.; Mahapatra, S.; Thapa, I.; Talmon, G.A.; Smith, L.M.; Yu, X.; Neelamegham, S.; Fu, J.; Xia, L.; Ponnusamy, M.P.; Batra, S.K. Disruption of C1galt1 gene promotes development and metastasis of pancreatic adenocarcinomas in mice. Gastroenterology, 2018, 155(5), 1608-1624.
[http://dx.doi.org/10.1053/j.gastro.2018.08.007] [PMID: 30086262]
[33]
Liu, F.; Fu, J.; Bergstrom, K.; Shan, X.; McDaniel, J.M.; McGee, S.; Bai, X.; Chen, W.; Xia, L. Core 1–derived mucin-type O-glycosylation protects against spontaneous gastritis and gastric cancer. J. Exp. Med., 2020, 217(1), e20182325.
[http://dx.doi.org/10.1084/jem.20182325] [PMID: 31645367]
[34]
Kuo, T.C.; Wu, M.H.; Yang, S.H.; Chen, S.T.; Hsu, T.W.; Jhuang, J.Y.; Liao, Y.Y.; Tien, Y.W.; Huang, M.C. C1GALT1 high expression is associated with poor survival of patients with pancreatic ductal adenocarcinoma and promotes cell invasiveness through integrin α v. Oncogene, 2021, 40(7), 1242-1254.
[http://dx.doi.org/10.1038/s41388-020-01594-4] [PMID: 33420364]
[35]
Jorgovanovic, D.; Song, M.; Wang, L.; Zhang, Y. Roles of IFN-γ in tumor progression and regression: A review. Biomark. Res., 2020, 8(1), 49.
[http://dx.doi.org/10.1186/s40364-020-00228-x] [PMID: 33005420]
[36]
Mendoza, J.L.; Escalante, N.K.; Jude, K.M.; Sotolongo Bellon, J.; Su, L.; Horton, T.M.; Tsutsumi, N.; Berardinelli, S.J.; Haltiwanger, R.S.; Piehler, J.; Engleman, E.G.; Garcia, K.C. Structure of the IFNγ receptor complex guides design of biased agonists. Nature, 2019, 567(7746), 56-60.
[http://dx.doi.org/10.1038/s41586-019-0988-7] [PMID: 30814731]
[37]
Maimela, N.R.; Liu, S.; Zhang, Y. Fates of CD8+ T cells in Tumor microenvironment. Comput. Struct. Biotechnol. J., 2019, 17, 1-13.
[http://dx.doi.org/10.1016/j.csbj.2018.11.004] [PMID: 30581539]
[38]
Karki, R.; Sharma, B.R.; Tuladhar, S.; Williams, E.P.; Zalduondo, L.; Samir, P.; Zheng, M.; Sundaram, B.; Banoth, B.; Malireddi, R.K.S.; Schreiner, P.; Neale, G.; Vogel, P.; Webby, R.; Jonsson, C.B.; Kanneganti, T.D. Synergism of TNF-α and IFN-γ triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes. Cell, 2021, 184(1), 149-168.e17.
[http://dx.doi.org/10.1016/j.cell.2020.11.025] [PMID: 33278357]
[39]
Jiang, Y. Wen, T.; Yan, R.; Kim, S.; Stowell, S.R.; Wang, W.; Wang, Y.; An, G.; Cummings, R.D.; Ju, T. O glycans on death receptors in cells modulate their sensitivity to TRAIL induced apoptosis through affecting on their stability and oligomerization. FASEB J., 2020, 34(9), 11786-11801.
[http://dx.doi.org/10.1096/fj.201900053RR] [PMID: 32692906]
[40]
Negishi, H.; Taniguchi, T.; Yanai, H. The interferon (IFN) class of cytokines and the IFN regulatory factor (IRF) transcription factor family. Cold Spring Harb. Perspect. Biol., 2018, 10(11), a028423.
[http://dx.doi.org/10.1101/cshperspect.a028423] [PMID: 28963109]
[41]
Wheelock, E.F. Interferon-like virus-inhibitor induced in human leukocytes by phytohemagglutinin. Science, 1965, 149(3681), 310-311.
[http://dx.doi.org/10.1126/science.149.3681.310] [PMID: 17838106]
[42]
Reading, J.L.; Gálvez-Cancino, F.; Swanton, C.; Lladser, A.; Peggs, K.S.; Quezada, S.A. The function and dysfunction of memory CD8 + T cells in tumor immunity. Immunol. Rev., 2018, 283(1), 194-212.
[http://dx.doi.org/10.1111/imr.12657] [PMID: 29664561]
[43]
Thompson, E.D.; Enriquez, H.L.; Fu, Y.X.; Engelhard, V.H. Tumor masses support naive T cell infiltration, activation, and differentiation into effectors. J. Exp. Med., 2010, 207(8), 1791-1804.
[http://dx.doi.org/10.1084/jem.20092454] [PMID: 20660615]
[44]
Seo, N.; Akiyoshi, K.; Shiku, H. Exosome mediated regulation of tumor immunology. Cancer Sci., 2018, 109(10), 2998-3004.
[http://dx.doi.org/10.1111/cas.13735] [PMID: 29999574]
[45]
Song, X.; Traub, B.; Shi, J.; Kornmann, M. Possible roles of interleukin 4 and 13 and their receptors in gastric and colon cancer. Int. J. Mol. Sci., 2021, 22(2), 727.
[http://dx.doi.org/10.3390/ijms22020727] [PMID: 33450900]
[46]
Gao, S.; Sugimura, R. The single cell level perspective of the tumor microenvironment and its remodeling by CAR-T cells. Cancer Treat. Res., 2022, 183, 275-285.
[http://dx.doi.org/10.1007/978-3-030-96376-7_10] [PMID: 35551664]
[47]
Shi, C.; Xu, X.; Yu, X.; Du, Z.; Luan, X.; Liu, D.; Hu, T. CD3/CD28 dynabeads induce expression of tn antigen in human t cells accompanied by hypermethylation of the cosmc promoter. Mol. Immunol., 2017, 90, 98-105.
[http://dx.doi.org/10.1016/j.molimm.2017.06.250] [PMID: 28708980]
[48]
de Haan, N.; Falck, D.; Wuhrer, M. Monitoring of immunoglobulin N- and O-glycosylation in health and disease. Glycobiology, 2020, 30(4), 226-240.
[http://dx.doi.org/10.1093/glycob/cwz048] [PMID: 31281930]
[49]
van Tol, W.; Wessels, H.; Lefeber, D.J. O-glycosylation disorders pave the road for understanding the complex human O-glycosylation machinery. Curr. Opin. Struct. Biol., 2019, 56, 107-118.
[http://dx.doi.org/10.1016/j.sbi.2018.12.006] [PMID: 30708323]
[50]
Scott, D.A.; Drake, R.R. Glycosylation and its implications in breast cancer. Expert Rev. Proteomics, 2019, 16(8), 665-680.
[http://dx.doi.org/10.1080/14789450.2019.1645604] [PMID: 31314995]
[51]
Berghuis, D.; Santos, S.J.; Baelde, H.J.; Taminiau, A.H.M.; Maarten Egeler, R.; Schilham, M.W.; Hogendoorn, P.C.W.; Lankester, A.C. Pro-inflammatory chemokine-chemokine receptor interactions within the Ewing sarcoma microenvironment determine CD8 + T-lymphocyte infiltration and affect tumour progression. J. Pathol., 2011, 223(3), 347-357.
[http://dx.doi.org/10.1002/path.2819] [PMID: 21171080]
[52]
Li, B.; Zhu, X.; Sun, L.; Yuan, L.; Zhang, J.; Li, H.; Ye, Z. Induction of a specific CD8+ T-cell response to cancer/testis antigens by demethylating pre-treatment against osteosarcoma. Oncotarget, 2014, 5(21), 10791-10802.
[http://dx.doi.org/10.18632/oncotarget.2505] [PMID: 25301731]
[53]
Yahiro, K.; Matsumoto, Y.; Yamada, H.; Endo, M.; Setsu, N.; Fujiwara, T.; Nakagawa, M.; Kimura, A.; Shimada, E.; Okada, S.; Oda, Y.; Nakashima, Y. Activation of TLR4 signaling inhibits progression of osteosarcoma by stimulating CD8-positive cytotoxic lymphocytes. Cancer Immunol. Immunother., 2020, 69(5), 745-758.
[http://dx.doi.org/10.1007/s00262-020-02508-9] [PMID: 32047957]
[54]
Fang, X.; Jiang, C.; Xia, Q. Effectiveness evaluation of dendritic cell immunotherapy for osteosarcoma on survival rate and in vitro immune response. Genet. Mol. Res., 2015, 14(4), 11763-11770.
[http://dx.doi.org/10.4238/2015.October.2.10] [PMID: 26436501]
[55]
Chen, H.; Cheng, H.; Liang, X.; Cai, S.; Liu, G. Immunosuppression reversal nanovaccines substituting dendritic cells for personalized cancer immunotherapy. Front. Immunol., 2022, 13, 934259.
[http://dx.doi.org/10.3389/fimmu.2022.934259] [PMID: 35812415]
[56]
Heymann, M.F.; Lézot, F.; Heymann, D. The contribution of immune infiltrates and the local microenvironment in the pathogenesis of osteosarcoma. Cell. Immunol., 2019, 343, 103711.
[http://dx.doi.org/10.1016/j.cellimm.2017.10.011] [PMID: 29117898]
[57]
Buskas, T.; Thompson, P.; Boons, G.J. Immunotherapy for cancer: Synthetic carbohydrate-based vaccines. Chem. Commun. , 2009, 36(36), 5335-5349.
[http://dx.doi.org/10.1039/b908664c] [PMID: 19724783]
[58]
Wu, Y.H.; Yang, C.Y.; Chien, W.L.; Lin, K.I.; Lai, M.Z. Removal of syndecan-1 promotes TRAIL-induced apoptosis in myeloma cells. J. Immunol., 2012, 188, 2914-2921.
[http://dx.doi.org/10.4049/jimmunol.1102065]
[59]
Igarashi, Y.; Sasada, T. Cancer vaccines: Toward the next breakthrough in cancer immunotherapy. J. Immunol. Res., 2020, 2020, 5825401.
[http://dx.doi.org/10.1155/2020/5825401] [PMID: 33282961]