Suppressive effects of tumor cell-derived 5′-deoxy-5′-methylthioadenosine on human T cells

OncoImmunology

Volumn 5, Issue 8, 2016, Pages

  Henrich, Frederik C ^a   Singer, Katrin ^a,b   Poller, Kerstin ^a   Bernhardt, Luise ^a   Strobl, Carolin D ^a   Limm, Katharina ^c   Ritter, Axel P ^d   Gottfried, Eva ^b   Völkl, Simon ^a   Jacobs, Benedikt ^a,e,f   Peter, Katrin ^b   Mougiakakos, Dimitrios ^a   Dettmer, Katja ^d   Oefner, Peter J ^d   Bosserhoff, Anja Katrin ^c   Kreutz, Marina P ^b   Aigner, Michael ^a   Mackensen, Andreas ^a  

^a UNIVERSITY HOSPITAL ERLANGEN   (Germany)

^b UNIVERSITY HOSPITAL REGENSBURG   (Germany)

^c UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^d UNIVERSITY OF REGENSBURG   (Germany)

^e OSLO UNIVERSITY HOSPITAL   (Norway)

^f UNIVERSITY OF OSLO   (Norway)

Author keywords

Antitumor immune response; cell signaling; immunosuppression; MTA; MTAP; protein methylation; T cells; tumor metabolism

Indexed keywords

5' METHYLTHIOADENOSINE; 5' METHYLTHIOADENOSINE PHOSPHORYLASE; CYCLIC AMP; GAMMA INTERFERON; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 1BETA; INTERLEUKIN 2; INTERLEUKIN 4; INTERLEUKIN 5; INTERLEUKIN 6; INTERLEUKIN 8; LYMPHOTOXIN; PROTEIN KINASE B; SYNAPTOPHYSIN; TUMOR NECROSIS FACTOR;

ANTIGEN SPECIFICITY; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER IMMUNOTHERAPY; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL CYCLE PROGRESSION; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL STIMULATION; CONTROLLED STUDY; CYTOTOXICITY; DENDRITIC CELL; EFFECTOR CELL; ELECTROSPRAY MASS SPECTROMETRY; ENZYME LINKED IMMUNOSORBENT ASSAY; FLOW CYTOMETRY; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; IMMUNE RESPONSE; IMMUNOASSAY; IMMUNOSUPPRESSIVE TREATMENT; LIQUID CHROMATOGRAPHY; PROTEIN METHYLATION; PROTEIN PHOSPHORYLATION; SANDWICH IMMUNOASSAY; SIGNAL TRANSDUCTION; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TANDEM MASS SPECTROMETRY; TUMOR ESCAPE; TUMOR IMMUNITY; WESTERN BLOTTING;

EID: 84982845418     PISSN: 21624011     EISSN: 2162402X     Source Type: Journal    
DOI: 10.1080/2162402X.2016.1184802     Document Type: Article

References (82)

1. D.Hanahan, R.A.Weinberg. Hallmarks of cancer:the next generation. Cell 2011; 144:646-74; PMID:21376230; http://dx.doi.org/10.1016/j.cell.2011.02.013
2. S.P.Kerkar, N.P.Restifo. Cellular constituents of immune escape within the tumor microenvironment. Cancer Res 2012; 72:3125-30; PMID:22721837; http://dx.doi.org/10.1158/0008-5472.CAN-11-4094
3. T.L.Whiteside. The tumor microenvironment and its role in promoting tumor growth. Oncogene 2008; 27:5904-12; PMID:18836471; http://dx.doi.org/10.1038/onc.2008.271
4. V.Bronte, S.Mocellin. Suppressive influences in the immune response to cancer. J Immunother 2009; 32:1-11; PMID:19307988; http://dx.doi.org/10.1097/CJI.0b013e3181837276
5. M.G.Vander Heiden, L.C.Cantley, C.B.Thompson. Understanding the Warburg effect:the metabolic requirements of cell proliferation. Science 2009; 324:1029-33; PMID:19460998; http://dx.doi.org/10.1126/science.1160809
6. G.Kroemer, J.Pouyssegur. Tumor cell metabolism:cancer's Achilles' heel. Cancer Cell 2008; 13:472-82; PMID:18538731; http://dx.doi.org/10.1016/j.ccr.2008.05.005
7. R.J.DeBerardinis, J.J.Lum, G.Hatzivassiliou, C.B.Thompson. The biology of cancer:metabolic reprogramming fuels cell growth and proliferation. Cell Metab 2008; 7:11-20; PMID:18177721; http://dx.doi.org/10.1016/j.cmet.2007.10.002
8. K.Fischer, P.Hoffmann, S.Voelkl, N.Meidenbauer, J.Ammer, M.Edinger, E.Gottfried, S.Schwarz, G.Rothe, S.Hoves et al. Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood 2007; 109:3812-9; PMID:17255361; http://dx.doi.org/10.1182/blood-2006-07-035972
9. K.Singer, E.Gottfried, M.Kreutz, A.Mackensen. Suppression of T-cell responses by tumor metabolites. Cancer Immunol Immunother 2011; 60:425-31; PMID:21240484; http://dx.doi.org/10.1007/s00262-010-0967-1
10. K.Singer, M.Kastenberger, E.Gottfried, C.G.Hammerschmied, M.Büttner, M.Aigner, B.Seliger, B.Walter, H.Schlösser, A.Hartmann et al. Warburg phenotype in renal cell carcinoma:high expression of glucose-transporter 1 (GLUT-1) correlates with low CD8(+) T-cell infiltration in the tumor. Int J Cancer 2011; 128:2085-95; PMID:20607826; http://dx.doi.org/10.1002/ijc.25543
11. A.Calcinotto, P.Filipazzi, M.Grioni, M.Iero, A.De Milito, A.Ricupito, A.Cova, R.Canese, E.Jachetti, M.Rossetti et al. Modulation of microenvironment acidity reverses anergy in human and murine tumor-infiltrating T lymphocytes. Cancer Res 2012; 72:2746-56; PMID:22593198; http://dx.doi.org/10.1158/0008-5472.CAN-11-1272
12. Y.Hori, H.Hori, Y.Yamada, C.J.Carrera, M.Tomonaga, S.Kamihira, D.A.Carson, T.Nobori. The methylthioadenosine phosphorylase gene is frequently co-deleted with the p16(INK4a) gene in acute type adult T-cell leukemia. Int J Cancer 1998; 75:51-6; PMID:9426690; http://dx.doi.org/10.1002/SICI(SICI)1097-0215(19980105)75:1%3c51::AID-IJC9%3e3.0.CO;2-0
13. I.Behrmann, S.Wallner, W.Komyod, P.C.Heinrich, M.Schuierer, R.Buettner, A.K.Bosserhoff. Characterization of methylthioadenosin phosphorylase (MTAP) expression in malignant melanoma. Am J Pathol 2003; 163:683-90; PMID:12875987; http://dx.doi.org/10.1016/S0002-9440(10)63695-4
14. S.A.Christopher, P.Diegelman, C.W.Porter, W.D.Kruger. Methylthioadenosine phosphorylase, a gene frequently codeleted with p16cdkN2a/ARF, acts as a tumor suppressor in a breast cancer cell line. Cancer Res 2002; 62:6639-44; PMID:12438261
15. C.Hellerbrand, M.Mühlbauer, S.Wallner, M.Schuierer, I.Behrmann, F.Bataille, T.Weiss, J.Schölmerich, A.K.Bosserhoff. Promoter-hypermethylation is causing functional relevant downregulation of methylthioadenosine phosphorylase (MTAP) expression in hepatocellular carcinoma. Carcinogenesis 2006; 27:64-72; PMID:16081515; http://dx.doi.org/10.1093/carcin/bgi201
16. C.J.Carrera, R.L.Eddy, T.B.Shows, D.A.Carson. Assignment of the gene for methylthioadenosine phosphorylase to human chromosome 9 by mouse-human somatic cell hybridization. Proc Natl Acad Sci U S A 1984; 81:2665-8; PMID:6425836; http://dx.doi.org/10.1073/pnas.81.9.2665
17. J.R.Bertino, W.R.Waud, W.B.Parker, M.Lubin. Targeting tumors that lack methylthioadenosine phosphorylase (MTAP) activity:Current strategies. Cancer Biol Ther 2011; 11:627-32; PMID:21301207; http://dx.doi.org/10.4161/cbt.11.7.14948
18. T.M.Savarese, D.L.Dexter, R.E.Parks. 5′-deoxy-5′-methylthioadenosine phosphorylase-II:Role of the enzyme in the metabolism and antineoplastic action of adenine-substituted analogs of 5′-deoxy-5’-methylthioadenosine. Biochem Pharmacol 1983; 32:1907-16; PMID:6411095; http://dx.doi.org/10.1016/0006-2952(83)90057-6
19. F.Bataille, G.Rogler, K.Modes, I.Poser, M.Schuierer, W.Dietmaier, P.Ruemmele, M.Mühlbauer, S.Wallner, C.Hellerbrand et al. Strong expression of methylthioadenosine phosphorylase (MTAP) in human colon carcinoma cells is regulated by TCF1/[beta]-catenin. Lab Invest 2005; 85:124-36; PMID:15492751; http://dx.doi.org/10.1038/labinvest.3700192
20. Y.Kadariya, B.Yin, B.Tang, S.A.Shinton, E.P.Quinlivan, X.Hua, A.Klein-Szanto, T.I.Al-Saleem, C.H.Bassing, R.R.Hardy, W.D.Kruger. Mice heterozygous for germ-line mutations in methylthioadenosine phosphorylase (MTAP) die prematurely of Tcell lymphoma. Cancer Res 2009; 69:5961-9; PMID:19567676; http://dx.doi.org/10.1158/0008-5472.CAN-09-0145
21. S.Meyer, P.J.Wild, T.Vogt, F.Bataille, C.Ehret, S.Gantner, M.Landthaler, M.Klinkhammer-Schalke, F.Hofstaedter, A.K.Bosserhoff. Methylthioadenosine phosphorylase represents a predictive marker for response to adjuvant interferon therapy in patients with malignant melanoma. Exp Dermatol 2010; 19:e251-7; PMID:20500769; http://dx.doi.org/10.1111/j.1600-0625.2010.01072.x
22. J.I.Toohey. Methylthio group cleavage from methylthioadenosine. Description of an enzyme and its relationship to the methylthio requirement of certain cells in culture. Biochem Biophys Res Commun 1977; 78:1273-80; PMID:921778; http://dx.doi.org/10.1016/0006-291X(77)91430-9
23. H.G.Williams-Ashman, J.Seidenfeld, P.Galletti. Trends in the biochemical pharmacology of 5′-deoxy-5'-methylthioadenosine. Biochem Pharmacol 1982; 31:277-88; PMID:6803807; http://dx.doi.org/10.1016/0006-2952(82)90171-X
24. M.A.Avila, E.R.García-Trevijano, S.C.Lu, F.J.Corrales, J.M.Mato. Methylthioadenosine. Int J Biochem Cell Biol 2004; 36:2125-30; PMID:15313459; http://dx.doi.org/10.1016/j.biocel.2003.11.016
25. N.Kamatani, D.A.Carson. Abnormal regulation of methylthioadenosine and polyamine metabolism in methylthioadenosine phosphorylase-deficient human leukemic cell lines. Cancer Res 1980; 40:4178-82; PMID:6781742
26. A.P.Stevens, B.Spangler, S.Wallner, M.Kreutz, K.Dettmer, P.J.Oefner, A.K.Bosserhoff. Direct and tumor microenvironment mediated influences of 5′deoxy-5′-(methylthio)adenosine on tumor progression of malignant melanoma. J Cell Biochem 2009; 106:210-9; PMID:19097084; http://dx.doi.org/10.1002/jcb.21984
27. K.Limm, C.Ott, S.Wallner, D.W.Mueller, P.Oefner, C.Hellerbrand, A.K.Bosserhoff. Deregulation of protein methylation in melanoma. Eur J Cancer 2013; 49:1305-13; PMID:23265702; http://dx.doi.org/10.1016/j.ejca.2012.11.026
28. G.Kirovski, A.P.Stevens, B.Czech, K.Dettmer, T.S.Weiss, P.Wild, A.Hartmann, A.K.Bosserhoff, P.J.Oefner, C.Hellerbrand. Down-regulation of methylthioadenosine phosphorylase (MTAP) induces progression of hepatocellular carcinoma via accumulation of 5’-deoxy-5'-methylthioadenosine (MTA). Am J Pathol 2011; 178:1145-52; PMID:21356366; http://dx.doi.org/10.1016/j.ajpath.2010.11.059
29. E.Ansorena, E.R.García-Trevijano, M.L.Martínez-Chantar, Z.Z.Huang, L.Chen, J.M.Mato, M.Iraburu, S.C.Lu, M.A.Avila. S-adenosylmethionine and methylthioadenosine are antiapoptotic in cultured rat hepatocytes but proapoptotic in human hepatoma cells. Hepatology 2002; 35:274-80; PMID:11826399; http://dx.doi.org/10.1053/jhep.2002.30419
30. P.Andreu-Pérez, J.Hernandez-Losa, T.Moliné, R.Gil, J.Grueso, A.Pujol, J.Cortés, M.A.Avila, J.A.Recio. Methylthioadenosine (MTA) inhibits melanoma cell proliferation and in vivo tumor growth. BMC Cancer 2010; 10:265; PMID:20529342; http://dx.doi.org/10.1186/1471-2407-10-265
31. A.Batova, H.Cottam, J.Yu, M.B.Diccianni, C.J.Carrera, A.L.Yu. EFA (9-β-D-erythrofuranosyladenine) is an effective salvage agent for methylthioadenosine phosphorylase-selective therapy of T-cell acute lymphoblastic leukemia with L-alanosine. Blood 2006; 107:898-903; PMID:16234352; http://dx.doi.org/10.1182/blood-2005-06-2430
32. M.M.Simile, S.Banni, E.Angioni, G.Carta, M.R.De Miglio, M.R.Muroni, D.F.Calvisi, A.Carru, R.M.Pascale, F.Feo. 5’-Methylthioadenosine administration prevents lipid peroxidation and fibrogenesis induced in rat liver by carbon-tetrachloride intoxication. J Hepatol 2001; 34:386-94; PMID:11322199; http://dx.doi.org/10.1016/S0168-8278(00)00078-7
33. V.Zappia, C.Zydek-Cwick, F.Schlenk. The specificity of S-adenosylmethionine derivatives in methyl transfer reactions. J Biol Chem 1969; 244:4499-509; PMID:4896753
34. K.J.Mavrakis, E.R.McDonaldIII, M.R.Schlabach, E.Billy, R.Gregory, D.A.Ruddy, K.Venkatesan, J.Yu, G.Mcallister, S.Ho et al. Disordered methionine metabolism in MTAP / CDKN2A deleted cancers leads to dependence on PRMT5. Science 2016; 351:1208; PMID:26912361; http://dx.doi.org/10.1126/science.aad5944
35. G.V.Kryukov, F.H.Wilson, J.R.Ruth, J.Paulk, A.Tsherniak, S.E.Marlow, F.Vazquez, B.A.Weir, M.E.Fitzgerald, M.Tanaka et al. MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells. Science 2016; 351:1214-8; PMID:26912360
36. H.Hevia, M.Varela-Rey, F.J.Corrales, C.Berasain, M.L.Martínez-Chantar, M.U.Latasa, S.C.Lu, J.M.Mato, E.R.García-Trevijano, M.A.Avila. 5’-methylthioadenosine modulates the inflammatory response to endotoxin in mice and in rat hepatocytes. Hepatology 2004; 39:1088-98; PMID:15057913; http://dx.doi.org/10.1002/hep.20154
37. E.Gottfried, K.Peter, M.P.Kreutz. The metabolic Achilles heel:tumor cell metabolism as therapeutic target. In From Molecular to Modular Tumor Therapy (pp. 111-132). Springer:Netherlands; http://dx.doi.org/10.1007/978-90-481-9531-2_7
38. V.Tardif, Y.Manenkova, M.Berger, K.Hoebe, J.P.Zuo, C.Yuan, D.H.Kono, A.N.Theofilopoulos, B.R.Lawson. Critical role of transmethylation in TLR signaling and systemic lupus erythematosus. Clin Immunol 2013; 147:133-43; PMID:23583916; http://dx.doi.org/10.1016/j.clim.2013.02.018
39. K.A.Mowen, B.T.Schurter, J.W.Fathman, M.David, L.H.Glimcher. Arginine methylation of NIP45 modulates cytokine gene expression in effector T lymphocytes. Mol Cell 2004; 15:559-71; PMID:15327772; http://dx.doi.org/10.1016/j.molcel.2004.06.042
40. B.Moreno, H.Hevia, M.Santamaria, J.Sepulcre, J.Muñoz, E.R.García-Trevijano, C.Berasain, F.J.Corrales, M.A.Avila, P.Villoslada. Methylthioadenosine reverses brain autoimmune disease. Ann Neurol 2006; 60:323-34; PMID:16786535; http://dx.doi.org/10.1002/ana.20895
41. M.L.Yang, A.J.P.Gee, R.J.Gee, C.I.Zurita-Lopez, S.Khare, S.G.Clarke, M.J.Mamula. Lupus autoimmunity altered by cellular methylation metabolism. Autoimmunity 2013; 46:21-31; PMID:23039363; http://dx.doi.org/10.3109/08916934.2012.732133
42. A.J.Ferro, A.A.Vandenbark, K.Marchitto. The role of 5’-methylthioadenosine phosphorylase in 5'-methylthioadenosine-mediated inhibition of lymphocyte transformation. Biochim Biophys Acta 1979; 588:294-301; PMID:116688; http://dx.doi.org/10.1016/0304-4165(79)90337-4
43. A.A.Vandenbark, A.J.Ferro, C.L.Barney. Inhibition of lymphocyte transformation by a naturally occurring metabolite:5′-methylthioadenosine. Cell Immunol 1980; 49:26-33; PMID:7351031; http://dx.doi.org/10.1016/0008-8749(80)90052-0
44. R.W.Wolford, M.R.MacDonald, B.Zehfus, T.J.Rogers, A.J.Feroo. Effect of 5′-methylthioadenosine and its analogs on murine lymphoid cell proliferation. Cancer Res 1981; 41:3035-9; PMID:6788366
45. M.W.White, A.A.Vandenbark, C.L.Barney, A.J.Ferro. Structural analogs of 5’-methylthioadenosine as substrates and inhibitors of 5'-methylthioadenosine phosphorylase and as inhibitors of human lymphocyte transformation. Biochem Pharmacol 1982; 31:503-7; PMID:6802139; http://dx.doi.org/10.1016/0006-2952(82)90151-4
46. L.Christa, L.Thuillier, J.P.Perignon. 5'-Deoxy-5'-methylthioadenosine inhibition of rat T lymphocyte phosphodiesterase:correlation with inhibition of Con A induced proliferation. Biochem Biophys Res Commun 1983; 113:425-32; PMID:6307288; http://dx.doi.org/10.1016/0006-291X(83)91743-6
47. F.Di Padova, C.Di Padova, G.Stramentinoli, R.Tritapepe. Inhibition of lymphocyte function by a naturally occurring nucleoside:5’-methylthioadenosine (MTA). Int J Immunopharmacol 1985; 7:193-8; PMID:4008139; http://dx.doi.org/10.1016/0192-0561(85)90026-8
48. B.B.Fredholm, M.Jondal, F.Lanefelt, J.Ng. Effect of 5'-methylthioadenosine, 3-deazaadenosine, and related compounds on human natural killer cell activity. Relation to cyclic AMP and methylation potential. Scand J Immunol 1984; 20:511-8; PMID:6096962; http://dx.doi.org/10.1111/j.1365-3083.1984.tb01033.x
49. A.Ohta, E.Gorelik, S.J.Prasad, F.Ronchese, D.Lukashev, M.K.K.Wong, X.Huang, S.Caldwell, K.Liu, P.Smith et al. A2A adenosine receptor protects tumors from antitumor T cells. Proc Natl Acad Sci U S A 2006; 103:13132-7; PMID:16916931; http://dx.doi.org/10.1073/pnas.0605251103
50. S.S.J.Sung, S.C.Silverstein. Inhibition of macrophage phagocytosis by methylation inhibitors lack of correlation of protein carboxymethylation and phospholipid methylation with phagocytosis. J Biol Chem 1985; 260:546-54; PMID:3871198
51. Y.Yang, M.T.Bedford. Protein arginine methyltransferases and cancer. Nat Rev Cancer 2013; 13:37-50; PMID:23235912; http://dx.doi.org/10.1038/nrc3409
52. T.B.Miranda, C.C.Cortez, C.B.Yoo, G.Liang, M.Abe, T.K.Kelly, V.E.Marquez, P.A.Jones. DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation. Mol Cancer Ther 2009; 8:1579-1588; PMID:19509260; http://dx.doi.org/10.1158/1535-7163.MCT-09-0013
53. F.Blanchet, A.Cardona, F.A.Letimier, M.S.Hershfield, O.Acuto. CD28 costimulatory signal induces protein arginine methylation in T cells. J Exp Med 2005; 202:371-7; PMID:16061726; http://dx.doi.org/10.1084/jem.20050176
54. P.Romero, P.R.Dunbar, D.Valmori, M.Pittet, G.S.Ogg, D.Rimoldi, J.L.Chen, D.Liénard, J.C.Cerottini, V.Cerundolo. Ex vivo staining of metastatic lymph nodes by class I major histocompatibility complex tetramers reveals high numbers of antigen-experienced tumor-specific cytolytic T lymphocytes. J Exp Med 1998; 188:1641-50; PMID:9802976; http://dx.doi.org/10.1084/jem.188.9.1641
55. D.J.Schendel, B.Gansbacher, R.Oberneder, M.Kriegmair, A.Hofstetter, G.Riethmüller, O.G.Segurado. Tumor-specific lysis of human renal cell carcinomas by tumor-infiltrating lymphocytes. I. HLA-A2-restricted recognition of autologous and allogeneic tumor lines. J Immunol 1993; 151:4209-20; PMID:8409397
56. K.R.Jerome, N.Domenech, O.J.Finn. Tumor-specific cytotoxic T cell clones from patients with breast and pancreatic adenocarcinoma recognize EBV-immortalized B cells transfected with polymorphic epithelial mucin complementary DNA. J Immunol 1993; 151:1654-62; PMID:8393050
57. A.Mackensen, N.Meidenbauer, S.Vogl, M.Laumer, J.Berger, R.Andreesen. Phase I study of adoptive T-cell therapy using antigen-specific CD8+ T cells for the treatment of patients with metastatic melanoma. J Clin Oncol 2006; 24:5060-9; PMID:17075125; http://dx.doi.org/10.1200/JCO.2006.07.1100
58. N.N.Hunder, H.Wallen, J.Cao, D.W.Hendricks, J.Z.Reilly, R.Rodmyre, A.Jungbluth, S.Gnjatic, J.A.Thompson, C.Yee. Treatment of metastatic melanoma with autologous CD4+ T cells against NY-ESO-1. N Engl J Med 2008; 358:2698-703; PMID:18565862; http://dx.doi.org/10.1056/NEJMoa0800251
59. S.A.Rosenberg, J.C.Yang, R.M.Sherry, U.S.Kammula, M.S.Hughes, G.Q.Phan, D.E.Citrin, N.P.Restifo, P.F.Robbins, J.R.Wunderlich et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res 2011; 17:4550-7; PMID:21498393; http://dx.doi.org/10.1158/1078-0432.CCR-11-0116
60. M.L.Disis, H.Bernhard, E.M.Jaffee. Use of tumour-responsive T cells as cancer treatment. Lancet 2009; 373:673-83; PMID:19231634; http://dx.doi.org/10.1016/S0140-6736(09)60404-9
61. I.Poschke, D.Mougiakakos, R.Kiessling. Camouflage and sabotage:Tumor escape from the immune system. Cancer Immunol Immunother 2011; 60:1161-71; PMID:21626032; http://dx.doi.org/10.1007/s00262-011-1012-8
62. E.Gottfried, M.Kreutz, A.Mackensen. Tumor metabolism as modulator of immune response and tumor progression. Semin Cancer Biol 2012; 22:335-41; PMID:22414910; http://dx.doi.org/10.1016/j.semcancer.2012.02.009
63. I.Kareva, P.Hahnfeldt. The emerging “Hallmarks” of metabolic reprogramming and immune evasion:distinct or linked? Cancer Res 2013; 73:2737-42; PMID:23423980; http://dx.doi.org/10.1158/0008-5472.CAN-12-3696
64. P.J.Wild, S.Meyer, M.Landthaler, F.Hofstaedter, A.K.Bosserhoff. A potential predictive marker for response to interferon in malignant melanoma. J Dtsch Dermatol Ges 2007; 5:456-9; PMID:17537037; http://dx.doi.org/10.1111/j.1610-0387.2007.06303.x
65. S.Radoja, M.Saio, D.Schaer, M.Koneru, S.Vukmanovic, A.B.Frey. CD8(+) tumor-infiltrating T cells are deficient in perforin-mediated cytolytic activity due to defective microtubule-organizing center mobilization and lytic granule exocytosis. J Immunol 2001; 167:5042-51; PMID:11673513; http://dx.doi.org/10.4049/jimmunol.167.9.5042
66. P.U.Prinz, A.N.Mendler, I.Masouris, L.Durner, R.Oberneder, E.Noessner. High DGK-α and disabled MAPK pathways cause dysfunction of human tumor-infiltrating CD8+ T cells that is reversible by pharmacologic intervention. J Immunol 2012; 188:5990-6000; PMID:22573804; http://dx.doi.org/10.4049/jimmunol.1103028
67. Y.Zheng, G.M.Delgoffe, C.F.Meyer, W.Chan, J.D.Powell. Anergic T cells are metabolically anergic. J Immunol 2009; 183:6095-101; PMID:19841171; http://dx.doi.org/10.4049/jimmunol.0803510
68. M.Huse. The T-cell-receptor signaling network. J Cell Sci 2009; 122:1269-73; PMID:19386893; http://dx.doi.org/10.1242/jcs.042762
69. M.Nyåkern, A.Cappellini, I.Mantovani, A.M.Martelli. Synergistic induction of apoptosis in human leukemia T cells by the Akt inhibitor perifosine and etoposide through activation of intrinsic and Fas-mediated extrinsic cell death pathways. Mol Cancer Ther 2006; 5:1559-70; PMID:16818515; http://dx.doi.org/10.1158/1535-7163.MCT-06-0076
70. D.W.Hoskin, J.S.Mader, S.J.Furlong, D.M.Conrad, J.Blay. Inhibition of T cell and natural killer cell function by adenosine and its contribution to immune evasion by tumor cells (Review). Int J Oncol 2008; 32:527-35; PMID:18292929
71. T.Iizasa, M.Kubota, D.A.Carson. Modulation of adenine nucleoside excretion and incorporation in adenosine deaminase deficient human lymphoma cells. Biochem Biophys Res Commun 1984; 121:514-20; PMID:6428410; http://dx.doi.org/10.1016/0006-291X(84)90212-2
72. M.S.Hershfield. New insights into adenosine-receptor-mediated immunosuppression and the role of adenosine in causing the immunodeficiency associated with adenosine deaminase deficiency. Eur J Immunol 2005; 35:25-30; PMID:15580654; http://dx.doi.org/10.1002/eji.200425738
73. F.Blanchet, B.T.Schurter, O.Acuto. Protein arginine methylation in lymphocyte signaling. Curr Opin Immunol 2006; 18:321-8; PMID:16616479; http://dx.doi.org/10.1016/j.coi.2006.03.001
74. R.V.Parry, S.G.Ward. Protein arginine methylation:a new handle on T lymphocytes? Trends Immunol 2010; 31:164-9; PMID:20181528; http://dx.doi.org/10.1016/j.it.2010.01.006
75. B.R.Lawson, T.Eleftheriadis, V.Tardif, R.Gonzalez-Quintial, R.Baccala, D.H.Kono, A.N.Theofilopoulos. Transmethylation in immunity and autoimmunity. Clin Immunol 2012; 143:8-21; PMID:22364920; http://dx.doi.org/10.1016/j.clim.2011.10.007
76. V.Geoghegan, A.Guo, D.Trudgian, B.Thomas, O.Acuto. Comprehensive identification of arginine methylation in primary T cells reveals regulatory roles in cell signalling. Nat Commun 2015; 6:6758; PMID:25849564; http://dx.doi.org/10.1038/ncomms7758
77. A.Dasgupta, K.-J.Jung, S.-J.Jeong, J.N.Brady. Inhibition of methyltransferases results in induction of g2/m checkpoint and programmed cell death in human T-lymphotropic virus type 1-transformed cells. J Virol 2008; 82:49-59; PMID:17942556; http://dx.doi.org/10.1128/JVI.01497-07
78. N.Meidenbauer, J.Marienhagen, M.Laumer, S.Vogl, J.Heymann, R.Andreesen, A.Mackensen. Survival and tumor localization of adoptively transferred melan-A-specific T cells in melanoma patients. J Immunol 2003; 170:2161-2169; PMID:12574389; http://dx.doi.org/10.4049/jimmunol.170.4.2161
79. S.Voelkl, T.V.Moore, M.Rehli, M.I.Nishimura, A.Mackensen, K.Fischer. Characterization of MHC class-I restricted TCRalphabeta+ CD4- CD8- double negative T cells recognizing the gp100 antigen from a melanoma patient after gp100 vaccination. Cancer Immunol Immunother 2009; 58:709-18; PMID:18836718; http://dx.doi.org/10.1007/s00262-008-0593-3
80. U.K.Laemmli. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227:680-5; PMID:5432063; http://dx.doi.org/10.1038/227680a0
81. A.P.Stevens, K.Dettmer, S.Wallner, A.K.Bosserhoff, P.J.Oefner. Quantitative analysis of 5’-deoxy-5'-methylthioadenosine in melanoma cells by liquid chromatography-stable isotope ratio tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2008; 876:123-8; PMID:18996776; http://dx.doi.org/10.1016/j.jchromb.2008.10.038
82. A.P.Stevens, K.Dettmer, G.Kirovski, K.Samejima, C.Hellerbrand, A.K.Bosserhoff, P.J.Oefner. Quantification of intermediates of the methionine and polyamine metabolism by liquid chromatography-tandem mass spectrometry in cultured tumor cells and liver biopsies. J Chromatogr A 2010; 1217:3282-8; PMID:20117790; http://dx.doi.org/10.1016/j.chroma.2010.01.025