{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T19:45:56Z","timestamp":1784231156199,"version":"3.55.0"},"reference-count":65,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["KFO262"],"award-info":[{"award-number":["KFO262"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Metabolite accumulation in the tumor microenvironment fosters immune evasion and limits the efficiency of immunotherapeutic approaches. Methylthioadenosine phosphorylase (MTAP), which catalyzes the degradation of 5\u2032-deoxy-5\u2032methylthioadenosine (MTA), is downregulated in many cancer entities. Consequently, MTA accumulates in the microenvironment of MTAP-deficient tumors, where it is known to inhibit tumor-infiltrating T cells and NK cells. However, the impact of MTA on other intra-tumoral immune cells has not yet been fully elucidated. To study the effects of MTA on dendritic cells (DCs), human monocytes were maturated into DCs with (MTA-DC) or without MTA (co-DC) and analyzed for activation, differentiation, and T cell-stimulating capacity. MTA altered the cytokine secretion profile of monocytes and impaired their maturation into dendritic cells. MTA-DCs produced less IL-12 and showed a more immature-like phenotype characterized by decreased expression of the co-stimulatory molecules CD80, CD83, and CD86 and increased expression of the monocyte markers CD14 and CD16. Consequently, MTA reduced the capability of DCs to stimulate T cells. Mechanistically, the MTA-induced effects on monocytes and DCs were mediated by a mechanism beyond adenosine receptor signaling. These results provide new insights into how altered polyamine metabolism impairs the maturation of monocyte-derived DCs and impacts the crosstalk between T and dendritic cells.<\/jats:p>","DOI":"10.3390\/cells13242114","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T07:42:18Z","timestamp":1734680538000},"page":"2114","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Tumor Metabolite 5\u2032-Deoxy-5\u2032Methylthioadenosine (MTA) Inhibits Maturation and T Cell-Stimulating Capacity of Dendritic Cells"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6035-2916","authenticated-orcid":false,"given":"Christina","family":"Brummer","sequence":"first","affiliation":[{"name":"Department of Internal Medicine III, University Hospital Regensburg, 93053 Regensburg, Germany"},{"name":"Bavarian Cancer Research Center (BZKF), 91054 Erlangen, 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Rev. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/s41591-018-0014-x","article-title":"Understanding the Tumor Immune Microenvironment (TIME) for Effective Therapy","volume":"24","author":"Binnewies","year":"2018","journal-title":"Nat. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.ccell.2023.02.016","article-title":"The Evolving Tumor Microenvironment: From Cancer Initiation to Metastatic Outgrowth","volume":"41","author":"Joyce","year":"2023","journal-title":"Cancer Cell"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Renner, K., Singer, K., Koehl, G.E., Geissler, E.K., Peter, K., Siska, P.J., and Kreutz, M. (2017). Metabolic Hallmarks of Tumor and Immune Cells in the Tumor Microenvironment. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00248"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.cmet.2016.08.011","article-title":"LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells","volume":"24","author":"Brand","year":"2016","journal-title":"Cell Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"927","DOI":"10.7150\/jca.27160","article-title":"5\u2032-Methylthioadenosine and Cancer: Old Molecules, New Understanding","volume":"10","author":"Li","year":"2019","journal-title":"J. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/s41568-019-0187-8","article-title":"Methionine Metabolism in Health and Cancer: A Nexus of Diet and Precision Medicine","volume":"19","author":"Sanderson","year":"2019","journal-title":"Nat. Rev. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"627","DOI":"10.4161\/cbt.11.7.14948","article-title":"Targeting Tumors That Lack Methylthioadenosine Phosphorylase (MTAP) Activity: Current Strategies","volume":"11","author":"Bertino","year":"2011","journal-title":"Cancer Biol. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/S0002-9440(10)63695-4","article-title":"Characterization of Methylthioadenosin Phosphorylase (MTAP) Expression in Malignant Melanoma","volume":"163","author":"Behrmann","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"35","DOI":"10.2217\/bmm-2017-0152","article-title":"Loss of MTAP Expression Is a Negative Prognostic Marker in Ewing Sarcoma Family of Tumors","volume":"12","author":"Antunes","year":"2018","journal-title":"Biomark. Med."},{"key":"ref_12","first-page":"782","article-title":"Methylthioadenosine Phosphorylase Gene Deletions Are Common in Osteosarcoma","volume":"8","author":"Villanueva","year":"2002","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_13","first-page":"1083","article-title":"Gene Deletion Chemoselectivity: Codeletion of the Genes for P16(INK4), Methylthioadenosine Phosphorylase, and the Alpha- and Beta-Interferons in Human Pancreatic Cell Carcinoma Lines and Its Implications for Chemotherapy","volume":"56","author":"Chen","year":"1996","journal-title":"Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7290","DOI":"10.1158\/1078-0432.CCR-04-0972","article-title":"Loss of Methylthioadenosine Phosphorylase and Elevated Ornithine Decarboxylase Is Common in Pancreatic Cancer","volume":"10","author":"Subhi","year":"2004","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1158\/1535-7163.MCT-05-0103","article-title":"Homozygous Deletions of Methylthioadenosine Phosphorylase in Human Biliary Tract Cancers","volume":"4","author":"Karikari","year":"2005","journal-title":"Mol. Cancer Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1002\/cam4.4971","article-title":"Genomic Landscape of Non-Small-Cell Lung Cancer with Methylthioadenosine Phosphorylase (MTAP) Deficiency","volume":"12","author":"Graziano","year":"2023","journal-title":"Cancer Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.lungcan.2008.04.019","article-title":"Immunohistochemical Diagnosis of Methylthioadenosine Phosphorylase (MTAP) Deficiency in Non-Small Cell Lung Carcinoma","volume":"63","author":"Watanabe","year":"2009","journal-title":"Lung Cancer Amst. Neth."},{"key":"ref_18","first-page":"1098","article-title":"Methylthioadenosine Phosphorylase Deficiency in Human Non-Small Cell Lung Cancers","volume":"53","author":"Nobori","year":"1993","journal-title":"Cancer Res."},{"key":"ref_19","first-page":"6639","article-title":"Methylthioadenosine Phosphorylase, a Gene Frequently Codeleted with P16(cdkN2a\/ARF), Acts as a Tumor Suppressor in a Breast Cancer Cell Line","volume":"62","author":"Christopher","year":"2002","journal-title":"Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.pathol.2021.05.101","article-title":"Expression and Localisation of Methylthioadenosine Phosphorylase (MTAP) in Oral Squamous Cell Carcinoma and Their Significance in Epithelial-to-Mesenchymal Transition","volume":"54","author":"Amano","year":"2022","journal-title":"Pathology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.bbadis.2004.08.002","article-title":"Methylthioadenosine Phosphorylase Gene Expression Is Impaired in Human Liver Cirrhosis and Hepatocarcinoma","volume":"1690","author":"Berasain","year":"2004","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1159\/000009983","article-title":"MTAP Gene Deletion in Endometrial Cancer","volume":"45","author":"Wong","year":"1998","journal-title":"Gynecol. Obstet. Invest."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1002\/jcb.21984","article-title":"Direct and Tumor Microenvironment Mediated Influences of 5\u2032-Deoxy-5\u2032-(Methylthio)Adenosine on Tumor Progression of Malignant Melanoma","volume":"106","author":"Stevens","year":"2009","journal-title":"J. Cell. Biochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1093\/carcin\/bgi201","article-title":"Promoter-Hypermethylation Is Causing Functional Relevant Downregulation of Methylthioadenosine Phosphorylase (MTAP) Expression in Hepatocellular Carcinoma","volume":"27","author":"Hellerbrand","year":"2006","journal-title":"Carcinogenesis"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e1184802","DOI":"10.1080\/2162402X.2016.1184802","article-title":"Suppressive Effects of Tumor Cell-Derived 5\u2019-Deoxy-5\u2019-Methylthioadenosine on Human T Cells","volume":"5","author":"Henrich","year":"2016","journal-title":"Oncoimmunology"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Jacobs, B., Schl\u00f6gl, S., Strobl, C.D., V\u00f6lkl, S., Stoll, A., Mougiakakos, D., Malmberg, K.-J., Mackensen, A., and Aigner, M. (2020). The Oncometabolite 5\u2032-Deoxy-5\u2032-Methylthioadenosine Blocks Multiple Signaling Pathways of NK Cell Activation. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.02128"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/imm.13587","article-title":"MTAP Deficiency Contributes to Immune Landscape Remodelling and Tumour Evasion","volume":"168","author":"Chang","year":"2023","journal-title":"Immunology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1038\/s41467-021-21804-1","article-title":"Tumor Methionine Metabolism Drives T-Cell Exhaustion in Hepatocellular Carcinoma","volume":"12","author":"Hung","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/0022-1759(96)00078-6","article-title":"Generation of Mature Dendritic Cells from Human Blood. An Improved Method with Special Regard to Clinical Applicability","volume":"196","author":"Romani","year":"1996","journal-title":"J. Immunol. Methods"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/82763","article-title":"IL-6 Switches the Differentiation of Monocytes from Dendritic Cells to Macrophages","volume":"1","author":"Chomarat","year":"2000","journal-title":"Nat. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/0006-2952(92)90616-Q","article-title":"Agonist Activity of 2- and 5\u2032-Substituted Adenosine Analogs and Their N6-Cycloalkyl Derivatives at A1\u2212 and A2\u2212adenosine Receptors Coupled to Adenylate Cyclase","volume":"43","author":"Daly","year":"1992","journal-title":"Biochem. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1016\/0006-2952(88)90560-6","article-title":"5\u2032-Deoxy-5\u2032-Methylthioadenosine: A Nucleoside Which Differentiates between Adenosine Receptor Types","volume":"37","author":"Munshi","year":"1988","journal-title":"Biochem. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/nrd2638","article-title":"Adenosine Receptors: Therapeutic Aspects for Inflammatory and Immune Diseases","volume":"7","author":"Linden","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.it.2003.11.003","article-title":"Adenosine: An Endogenous Regulator of Innate Immunity","volume":"25","author":"Cronstein","year":"2004","journal-title":"Trends Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1016\/j.ccell.2023.09.005","article-title":"Enzyme-Mediated Depletion of Methylthioadenosine Restores T Cell Function in MTAP-Deficient Tumors and Reverses Immunotherapy Resistance","volume":"41","author":"Gjuka","year":"2023","journal-title":"Cancer Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1158\/1535-7163.MCT-19-0189","article-title":"Selective PRMT5 Inhibitors Suppress Human CD8+ T Cells by Upregulation of P53 and Impairment of the AKT Pathway Similar to the Tumor Metabolite MTA","volume":"19","author":"Strobl","year":"2020","journal-title":"Mol. Cancer Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.celrep.2016.03.043","article-title":"MTAP Deletions in Cancer Create Vulnerability to Targeting of the MAT2A\/PRMT5\/RIOK1 Axis","volume":"15","author":"Marjon","year":"2016","journal-title":"Cell Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1038\/s41419-020-03175-5","article-title":"Cancer Cell Metabolic Reprogramming: A Keystone for the Response to Immunotherapy","volume":"11","author":"Cerezo","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.ccell.2023.01.009","article-title":"Metabolic Programming and Immune Suppression in the Tumor Microenvironment","volume":"41","author":"Arner","year":"2023","journal-title":"Cancer Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2120676","DOI":"10.1080\/2162402X.2022.2120676","article-title":"Immunosuppressive Tumor Microenvironment Modulation by Chemotherapies and Targeted Therapies to Enhance Immunotherapy Effectiveness","volume":"11","author":"Barnestein","year":"2022","journal-title":"Oncoimmunology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0192-0561(85)90026-8","article-title":"Inhibition of Lymphocyte Function by a Naturally Occurring Nucleoside: 5\u2032-Methylthioadenosine (MTA)","volume":"7","author":"Stramentinoli","year":"1985","journal-title":"Int. J. Immunopharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Can\u00e8, S., Ugel, S., Trovato, R., Marigo, I., De Sanctis, F., Sartoris, S., and Bronte, V. (2019). The Endless Saga of Monocyte Diversity. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01786"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.4049\/jimmunol.0902584","article-title":"Lactic Acid and Acidification Inhibit TNF Secretion and Glycolysis of Human Monocytes","volume":"184","author":"Dietl","year":"2010","journal-title":"J. Immunol."},{"key":"ref_44","first-page":"1674","article-title":"Tumor-Induced Regulation of Suppressor Macrophage Nitric Oxide and TNF-Alpha Production. Role of Tumor-Derived IL-10, TGF-Beta, and Prostaglandin E2","volume":"153","author":"Alleva","year":"1994","journal-title":"J. Immunol. Baltim. Md 1950"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.cytogfr.2007.10.008","article-title":"Tumor-Induced Modulation of Dendritic Cell Function","volume":"19","author":"Gottfried","year":"2008","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.immuni.2006.04.017","article-title":"Migratory Dendritic Cells Transfer Antigen to a Lymph Node-Resident Dendritic Cell Population for Efficient CTL Priming","volume":"25","author":"Allan","year":"2006","journal-title":"Immunity"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/imr.12432","article-title":"Dendritic Cell Maturation and Cross-presentation: Timing Matters!","volume":"272","author":"Alloatti","year":"2016","journal-title":"Immunol. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s10555-006-9010-6","article-title":"Intratumoral Cytokines\/Chemokines\/Growth Factors and Tumor Infiltrating Dendritic Cells: Friends or Enemies?","volume":"25","author":"Shurin","year":"2006","journal-title":"Cancer Metastasis Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1084\/jem.190.10.1417","article-title":"In Breast Carcinoma Tissue, Immature Dendritic Cells Reside within the Tumor, Whereas Mature Dendritic Cells Are Located in Peritumoral Areas","volume":"190","author":"Bell","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1182\/blood-2005-05-1795","article-title":"Tumor-Derived Lactic Acid Modulates Dendritic Cell Activation and Antigen Expression","volume":"107","author":"Gottfried","year":"2006","journal-title":"Blood"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5479","DOI":"10.1158\/0008-5472.CAN-06-3963","article-title":"Elevated Interleukin-6 and G-CSF in Human Pancreatic Cancer Cell Conditioned Medium Suppress Dendritic Cell Differentiation and Activation","volume":"67","author":"Bharadwaj","year":"2007","journal-title":"Cancer Res."},{"key":"ref_52","first-page":"1439","article-title":"Novel Immunosuppressive Properties of Interleukin-6 in Dendritic Cells: Inhibition of NF-kappaB Binding Activity and CCR7 Expression","volume":"18","author":"Hegde","year":"2004","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1111\/j.1365-2249.2008.03853.x","article-title":"CD1a Expression Defines an Interleukin-12 Producing Population of Human Dendritic Cells","volume":"155","author":"Cernadas","year":"2009","journal-title":"Clin. Exp. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1001\/archotol.124.6.641","article-title":"Peritumoral CD1a-Positive Dendritic Cells Are Associated with Improved Survival in Patients with Tongue Carcinoma","volume":"124","author":"Goldman","year":"1998","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1053\/hupa.2001.26455","article-title":"Expression of Dendritic Cells in Ovarian Tumors Correlates with Clinical Outcome in Patients with Ovarian Cancer","volume":"32","author":"Eisenthal","year":"2001","journal-title":"Hum. Pathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/sj.bjc.6601114","article-title":"CD1a-Positive Infiltrating-Dendritic Cell Density and 5-Year Survival from Human Breast Cancer","volume":"89","author":"Coventry","year":"2003","journal-title":"Br. J. Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1002\/ijc.10915","article-title":"Prognostic Value of Tumor-Infiltrating Dendritic Cells Expressing CD83 in Human Breast Carcinomas","volume":"104","author":"Iwamoto","year":"2003","journal-title":"Int. J. Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.it.2004.03.002","article-title":"CD1a in Human Cancers: A New Role for an Old Molecule","volume":"25","author":"Coventry","year":"2004","journal-title":"Trends Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Embgenbroich, M., and Burgdorf, S. (2018). Current Concepts of Antigen Cross-Presentation. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01643"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Li, Z., Ju, X., Silveira, P.A., Abadir, E., Hsu, W.-H., Hart, D.N.J., and Clark, G.J. (2019). CD83: Activation Marker for Antigen Presenting Cells and Its Therapeutic Potential. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01312"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1158\/2326-6066.CIR-13-0120-T","article-title":"Polyamine-Blocking Therapy Reverses Immunosuppression in the Tumor Microenvironment","volume":"2","author":"Hayes","year":"2014","journal-title":"Cancer Immunol. Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Abakushina, E.V., Popova, L.I., Zamyatnin, A.A., Werner, J., Mikhailovsky, N.V., and Bazhin, A.V. (2021). The Advantages and Challenges of Anticancer Dendritic Cell Vaccines and NK Cells in Adoptive Cell Immunotherapy. Vaccines, 9.","DOI":"10.3390\/vaccines9111363"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Hansen, L.J., Yang, R., Roso, K., Wang, W., Chen, L., Yang, Q., Pirozzi, C.J., and He, Y. (2022). MTAP Loss Correlates with an Immunosuppressive Profile in GBM and Its Substrate MTA Stimulates Alternative Macrophage Polarization. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-07697-0"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.ajpath.2010.11.059","article-title":"Down-Regulation of Methylthioadenosine Phosphorylase (MTAP) Induces Progression of Hepatocellular Carcinoma via Accumulation of 5\u2032-Deoxy-5\u2032-Methylthioadenosine (MTA)","volume":"178","author":"Kirovski","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1016\/j.ejca.2012.11.026","article-title":"Deregulation of Protein Methylation in Melanoma","volume":"49","author":"Limm","year":"2013","journal-title":"Eur. J. 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