药学学报, 2019, 54(3): 407-419
姜洪丽, 蒋学阳, 汤同中, 柳文媛, 冯锋, 孙昊鹏, 曲玮. 干预肿瘤代谢的新策略:氨基酸代谢的调控途径及其药物研究进展[J]. 药学学报, 2019, 54(3): 407-419.
JIANG Hong-li, JIANG Xue-yang, TANG Tong-zhong, LIU Wen-yuan, FENG Feng, SUN Hao-peng, QU Wei. A new strategy to intervene tumor metabolism: regulatory targets for amino acid metabolism and advances in drug research[J]. Acta Pharmaceutica Sinica, 2019, 54(3): 407-419.

姜洪丽1, 蒋学阳1, 汤同中1, 柳文媛2, 冯锋1, 孙昊鹏3, 曲玮1
1. 中国药科大学天然药物化学教研室, 江苏 南京 210000;
2. 中国药科大学药物分析教研室, 江苏 南京 210000;
3. 中国药科大学药物化学系, 江苏 南京 210000
关键词:    氨基酸代谢      肿瘤      谷氨酰胺      丝氨酸      色氨酸      代谢通路      活性分子     
A new strategy to intervene tumor metabolism: regulatory targets for amino acid metabolism and advances in drug research
JIANG Hong-li1, JIANG Xue-yang1, TANG Tong-zhong1, LIU Wen-yuan2, FENG Feng1, SUN Hao-peng3, QU Wei1
1. School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210000, China;
2. Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210000, China;
3. Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210000, China
Reprogramming of metabolism is one of the most critical features in tumorigenesis and tumor growth. Many types of cancer show an increased demand for specific amino acids, rely on exogenous supplies, or alter amino acid metabolic pathways, leading to changes in corresponding amino acid levels to meet the need of tumorigenesis. Therefore, if the level of tumor growth-dependent amino acids can be effectively controlled, a new treatment strategy can be developed from the perspective of cell metabolism. At present, remarkable progress has been made in this field. This paper outlines the amino acid metabolic pathways closely related to tumorigenesis and tumor growth, and summarizes the corresponding regulatory mechanisms and active molecules. Finally, the direction of the field is discussed and prospected for future development.
Key words:    amino acid metabolism    cancer    glutamine    serine    tryptophan    metabolic pathway    active molecular   
收稿日期: 2018-10-23
DOI: 10.16438/j.0513-4870.2018-0969
基金项目: 国家自然科学基金资助项目(81573281);中国药科大学"双一流"建设团队项目资助(CPU2018GF11,CPU2018GY34).
通讯作者: 孙昊鹏, 曲玮
Email: sunhaopeng@163.com;popoqzh@126.com
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[1] Pavlova NN, Thompson CB. The emerging hallmarks of cancer metabolism[J]. Cell Metab, 2016, 23:27-47.
[2] Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism[J]. Nat Rev Cancer, 2011, 11:85-95.
[3] Cantor JR, Sabatini DM. Cancer cell metabolism:one hallmark, many faces[J]. Cancer Discov, 2012, 2:881-898.
[4] Warburg O, Wind F, Negelein E. The metabolism of tumors in the body[J]. J Gen Physiol, 1927, 8:519-530.
[5] Warburg O. On the origin of cancer cells[J]. Science, 1956, 123:309-314.
[6] Choi J, Kim ES, Koo JS. Expression of pentose phosphate pathway-related proteins in breast cancer[J]. Dis Markers, 2018, 2018:9369358.
[7] Shuvalov O, Petukhov A, Daks A, et al. One-carbon metabolism and nucleotide biosynthesis as attractive targets for anticancer therapy[J]. Oncotarget, 2017, 8:23955-23977.
[8] Santos CR, Schulze A. Lipid metabolism in cancer[J]. FEBS J, 2012, 279:2610-2623.
[9] Hanahan D, Weinberg Robert A. Hallmarks of cancer:the next generation[J]. Cell, 2011, 144:646-674.
[10] Lukey MJ, Katt WP, Cerione RA. Targeting amino acid metabolism for cancer therapy[J]. Drug Discov Today, 2016, 6:281-289.
[11] Dillon BJ, Prieto VG, Curley SA, et al. Incidence and distribution of argininosuccinate synthetase deficiency in human cancers[J]. Cancer, 2004, 100:826-833.
[12] Qiu F, Huang J, Sui M. Targeting arginine metabolism pathway to treat arginine-dependent cancers[J]. Cancer Lett, 2015, 364:1-7.
[13] Takaku H, Takase M, Abe SI, et al. In vivo anti-tumor activity of arginine deiminase purified from Mycoplasma arginine[J]. Int J Cancer, 1992, 51:244-249.
[14] Sezgin N, Torun T, Yalcin F. Biochemical characterization of the arginine degrading enzymes arginase and arginine deiminase and their effect on nitric oxide production[J]. Med Sci Monit, 2002, 8:BR248-BR253.
[15] Kraemer PM, Defend V, Hayflick L, et al. Mycoplasma (PPLO) strains with lytic activity for murine lymphoma cells in vitro[J]. Proc Soc Exp Biol Med, 1963, 112:381-387.
[16] Ni Y, Schwaneberg U, Sun ZH. Arginine deiminase, a potential anti-tumor drug[J]. Cancer Lett, 2008, 261:1-11.
[17] Holtsberg FW, Ensor CM, Steiner MR, et al. Poly (ethylene glycol) (PEG) conjugated arginine deiminase:effects of PEG formulations on its pharmacological properties[J]. J Control Release, 2002, 80:259-271.
[18] Kim RH, Coates JM, Bowles TL, et al. Arginine deiminase as a novel therapy for prostate cancer induces autophagy and caspase-independent apoptosis[J]. Cancer Res, 2009, 69:700-708.
[19] Syed N, Langer J, Janczar K, et al. Epigenetic status of argininosuccinate synthetase and argininosuccinate lyase modulates autophagy and cell death in glioblastoma[J]. Cell Death Dis, 2013, 4:e458.
[20] Huang HY, Wu WR, Wang YH, et al. ASS1 as a novel tumor suppressor gene in myxofibrosarcomas:aberrant loss via epigenetic DNA methylation confers aggressive phenotypes, negative prognostic impact, and therapeutic relevance[J]. Clin Cancer Res, 2013, 19:2861-2872.
[21] Huang CC, Tsai ST, Kuo CC, et al. Arginine deprivation as a new treatment strategy for head and neck cancer[J]. Oral Oncology, 2012, 48:1227-1235.
[22] Feun LG, Marini A, Walker G, et al. Negative argininosuccinate synthetase expression in melanoma tumors may predict clinical benefit from arginine-depleting therapy with pegylated arginine deiminase[J]. Br J Cancer, 2012, 106:1481-1485.
[23] Bowles TL, Kim R, Galante J, et al. Pancreatic cancer cell lines deficient in argininosuccinate synthetase are sensitive to arginine deprivation by arginine deiminase[J]. Int J Cancer, 2008, 123:1950-1955.
[24] Glazer ES, Piccirillo M, Albino V, et al. Phase Ⅱ study of pegylated arginine deiminase for nonresectable and metastatic hepatocellular carcinoma[J]. J Clin Oncol, 2010, 28:2220-2226.
[25] Noh EJ, Kang SW, Shin YJ, et al. Arginine deiminase enhances dexamethasone-induced cytotoxicity in human T-lymphoblastic leukemia CCRF-CEM cells[J]. Int J Cancer, 2004, 112:502-508.
[26] Allen MD, Luong P, Hudson C, et al. Prognostic and therapeutic impact of argininosuccinate synthetase 1 control in bladder cancer as monitored longitudinally by PET imaging[J]. Cancer Res, 2014, 74:896-907.
[27] Qiu F, Chen YR, Liu X, et al. Arginine starvation impairs mitochondrial respiratory function in ASS1-deficient breast cancer cells[J]. Sci Signal, 2014, 7:ra31.
[28] You M, Savaraj N, Wangpaichitr M, et al. The combination of ADI-PEG20 and TRAIL effectively increases cell death in melanoma cell lines[J]. Biochem Biophys Res Commun, 2010, 394:760-766.
[29] Kim JE, Kim SY, Lee KW, et al. Arginine deiminase originating from Lactococcus lactis ssp. lactis American Type Culture Collection (ATCC) 7962 induces G1-phase cell-cycle arrest and apoptosis in SNU-1 stomach adenocarcinoma cells[J]. Br J Nutr, 2009, 102:1469-1476.
[30] Haines RJ, Pendleton LC, Eichler DC. Argininosuccinate synthase:at the center of arginine metabolism[J]. Int J Biochem Cell Biol, 2011, 2:8-23.
[31] Delage B, Luong P, Maharaj L, et al. Promoter methylation of argininosuccinate synthetase-1 sensitises lymphomas to arginine deiminase treatment, autophagy and caspase-dependent apoptosis[J]. Cell Death Dis, 2012, 3:e342.
[32] Sicinschi LA, Lopezcarrillo L, Camargo MC, et al. Gastric cancer risk in a Mexican population:role of Helicobacter pylori CagA positive infection and polymorphisms in interleukin-1 and -10 genes[J]. Int J Cancer, 2010, 118:649-657.
[33] Lam TL, Wong GKY, Chong HC, et al. Recombinant human arginase inhibits proliferation of human hepatocellular carcinoma by inducing cell cycle arrest[J]. Cancer Lett, 2009, 277:91-100.
[34] Morrow K, Hernandez CP, Raber P, et al. Anti-leukemic mechanisms of pegylated arginase I in acute lymphoblastic T-cell leukemia[J]. Leukemia, 2013, 27:569-577.
[35] Bhutia YD, Babu E, Ramachandran S, et al. Amino acid transporters in cancer and their relevance to "glutamine addiction":novel targets for the design of a new class of anticancer drugs[J]. Cancer Res, 2015, 75:1782-1788.
[36] Coothankandaswamy V, Cao S, Xu Y, et al. Amino acid transporter SLC6A14 is a novel and effective drug target for pancreatic cancer[J]. Br J Pharmacol, 2016, 173:3292-3306.
[37] Nicklin P, Bergman P, Zhang B,et al. Bidirectional transport of amino acids regulates mTOR and autophagy[J]. Cell, 2009, 136:521-534.
[38] Gross MI,Demo SD, Dennison JB, et al. Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer[J]. Mol Cancer Ther, 2014, 13:890-901.
[39] Gao P, Tchernyshyov I, Chang TC, et al. c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism[J]. Nature, 2009, 458:762-765.
[40] Wang JB, Erickson JW, Fuji R, et al. Targeting mitochondrial glutaminase activity inhibits oncogenic transformation[J]. Cancer Cell, 2010, 18:207-219.
[41] Altman BJ, Stine ZE, Dang CV. From Krebs to clinic:glutamine metabolism to cancer therapy[J]. Nat Rev Cancer, 2016, 16:619-634.
[42] Coloff JL, Murphy JP, Braun CR, et al. Differential glutamate metabolism in proliferating and quiescent mammary epithelial cells[J]. Cell Metab, 2016, 23:867-880.
[43] Jin L, Li D, Alesi N, et al. Glutamate dehydrogenase 1 signals through antioxidant glutathione peroxidase 1 to regulate redox homeostasis and tumor growth[J]. Cancer Cell, 2015, 27:257-270.
[44] Zhang C, Yuan XR, Li HY, et al. Anti-cancer effect of metabotropic glutamate receptor 1 inhibition in human glioma U87 cells:involvement of PI3K/Akt/mTOR pathway[J]. Cell Physiol Biochem, 2015, 35:419-432.
[45] Lukey MJ, Wilson KF, Cerione RA. Therapeutic strategies impacting cancer cell glutamine metabolism[J]. Future Med Chem, 2013, 5:1685-1700.
[46] Wang JB, Erickson JW, Fuji R, et al. Targeting mitochondrial glutaminase activity inhibits oncogenic transformation[J]. Cancer Cell, 2010, 18:207-219.
[47] Xiang Y, Stine ZE, Xia J, et al. Targeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis[J]. J Clin Invest, 2015, 125:2293-2306.
[48] Simpson NE, Tryndyak VP, Beland FA, et al. An in vitro investigation of metabolically sensitive biomarkers in breast cancer progression[J]. Breast Cancer Res Treat, 2012, 133:959-968.
[49] Martínrufián M, Nascimentogomes R, Higuero A, et al. Both GLS silencing and GLS2 overexpression synergize with oxidative stress against proliferation of glioma cells[J]. J Mol Med, 2014, 92:277-290.
[50] Mohamed A, Deng X, Khuri FR, et al. Altered glutamine metabolism and therapeutic opportunities for lung cancer[J]. Clin Lung Cancer, 2014, 15:7-15.
[51] Simpson NE, Tryndyak VP, Pogribna M, et al. Modifying metabolically sensitive histone marks by inhibiting glutamine metabolism affects gene expression and alters cancer cell phenotype[J]. Epigenetics, 2012, 7:1413-1420.
[52] Yuan L, Sheng X, Clark LH, et al. Glutaminase inhibitor compound 968 inhibits cell proliferation and sensitizes paclitaxel in ovarian cancer[J]. Am J Transl Res, 2016, 8:4265-4277.
[53] Yan YS, Hui L, Zhang X, et al. Histone modifications in senescence-associated resistance to apoptosis by oxidative stress[J]. Redox Biol, 2013, 1:8-16.
[54] Friday RE, Oliver R, Welbourne T, et al. Directing glutamine and glucose metabolism with troglitazone and EGCG limits MCF-7 cell growth:Proceedings of the 101st Annual Meeting of the American Association for Cancer Research[C]. Washington, 2010:48.
[55] Zhang J, Wang G, Mao Q, et al. Glutamate dehydrogenase (GDH) regulates bioenergetics and redox homeostasis in human glioma[J]. Oncotarget, 2016, 295:799-800.
[56] Korangath P, Teo WW, Sadik H, et al. Targeting glutamine metabolism in breast cancer with aminooxyacetate[J]. Clin Cancer Res, 2015, 21:3263-3273.
[57] Papathanassiu AE, Hong AV. Inhibition of BCAT1 suppresses the expression of pro-metastatic proteins and reduces cancer metastasis:proceedings of the 105th Annual Meeting of the American Association for Cancer Research[C]. San Diego:AACR, 2014:2683.
[58] Mayers JR, Torrence ME, Danai LV, et al. Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras-driven cancers[J]. Science, 2016, 353:1161-1165.
[59] Esslinger CS, Cybulski KA, Rhoderick JF. Nγ-Aryl glutamine analogues as probes of the ASCT2 neutral amino acid transporter binding site[J]. Bioorg Med Chem, 2005, 13:1111-1118.
[60] Oppedisano F, Catto M, Koutentis PA, et al. Inactivation of the glutamine/amino acid transporter ASCT2 by 1,2,3-dithiazoles:proteoliposomes as a tool to gain insights in the molecular mechanism of action and of antitumor activity[J]. Toxicol Appl Pharmacol, 2012, 265:93-102.
[61] Schulte ML, Khodadadi AB, Cuthbertson ML, et al. 2-Amino-4-bis(aryloxybenzyl)aminobutanoic acids:a novel scaffold for inhibition of ASCT2-mediated glutamine transport[J]. Bioorg Med Chem Lett, 2016, 26:1044-1047.
[62] Bröer A, Fairweather S, Bröer S. Disruption of amino acid homeostasis by novel ASCT2 inhibitors involves multiple targets[J]. Front Pharmacol, 2018, 9:785.
[63] Shanware NP, Mullen AR, Deberardinis RJ, et al. Glutamine:pleiotropic roles in tumor growth and stress resistance[J]. J Mol Med, 2011, 89:229-236.
[64] Speyer CL, Nassar MA, Hachem AH, et al. Riluzole mediates anti-tumor properties in breast cancer cells independent of metabotropic glutamate receptor-1[J]. Breast Cancer Res Treat, 2016, 157:217-228.
[65] Possemato R, Marks KM, Shaul YD, et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer[J]. Nature, 2011, 476:346-350.
[66] Denicola GM, Chen PH, Mullarky E, et al. NRF2 regulates serine biosynthesis in non-small cell lung cancer[J]. Nat Genet, 2015, 47:1475-1481.
[67] Pollari S, Käkönen SM, Edgren H, et al. Enhanced serine production by bone metastatic breast cancer cells stimulates osteoclastogenesis[J]. Breast Cancer Res Treat, 2011, 125:421-430.
[68] Maddocks ODK, Berkers CR, Mason SM, et al. Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells[J]. Nature, 2013, 493:542-546.
[69] Yang M, Vousden KH. Serine and one-carbon metabolism in cancer[J]. Nat Rev Cancer, 2016, 16:650-652.
[70] Nilsson LM, Forshell TZP, Rimpi S, et al. Mouse genetics suggests cell-context dependency for Myc-regulated metabolic enzymes during tumorigenesis[J]. PLoS Genet, 2012, 8:e1002573.
[71] Nilsson R, Jain M, Madhusudhan N, et al. Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer[J]. Nat Commun, 2014, 5:3128.
[72] Zhang WC, Shyh-Chang N, Yang H, et al. Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis[J]. Cell, 2012, 148:259-272.
[73] Pacold ME, Brimacombe KR, Chan SH, et al. A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate[J]. Nat Chem Biol, 2016, 12:452-458.
[74] Mullarky E, Lucki NC, Zavareh RB, et al. Identification of a small molecule inhibitor of 3-phosphoglycerate dehydrogenase to target serine biosynthesis in cancers[J]. Proc Natl Acad Sci U S A, 2016, 113:1778-1783.
[75] Vacchelli E, Aranda F, Eggermont A, et al. Trial watch:IDO inhibitors in cancer therapy[J]. Oncoimmunology, 2014, 3:e957994.
[76] Miller CL, Llenos IC, Dulay JR, et al. Upregulation of the initiating step of the kynurenine pathway in postmortem anterior cingulate cortex from individuals with schizophrenia and bipolar disorder[J]. Brain Res, 2006, 1073:25-37.
[77] Pilotte L, Larrieu P, Stroobant V, et al. Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase[J]. Proc Natl Acad Sci U S A, 2012, 109:2497-2502.
[78] Yamamoto S, Hayaishi O. Tryptophan pyrrolase of rabbit intestine. D-and L-tryptophan-cleaving enzyme or enzymes[J]. J Biol Chem, 1967, 242:5260-5266.
[79] Cady SG, Sono M. 1-Methyl-DL-tryptophan, beta-(3-benzofuranyl)-DL-alanine (the oxygen analog of tryptophan), and beta-[3-benzo(b)thienyl]-DL-alanine (the sulfur analog of tryptophan) are competitive inhibitors for indoleamine 2,3-dioxygenase[J]. Arch Biochem Biophys, 1991, 291:326-333.
[80] Kudo Y, Boyd CAR. The role of L-tryptophan transport in L-tryptophan degradation by indoleamine 2,3-dioxygenase in human placental explants[J]. J Physiol, 2010, 531:417-423.
[81] Metz R, Rust S, Duhadaway JB, et al. IDO inhibits a tryptophan sufficiency signal that stimulates mTOR:a novel IDO effector pathway targeted by D-1-methyl-tryptophan[J]. Oncoimmunology, 2012, 1:1460-1468.
[82] Yue EW, Douty B, Wayland B, et al. Discovery of potent competitive inhibitors of indoleamine 2,3-dioxygenase with in vivo pharmacodynamic activity and efficacy in a mouse melanoma model[J]. J Med Chem, 2009, 52:7364-7367.
[83] Austin CJD, Rendina LM. Targeting key dioxygenases in tryptophan-kynurenine metabolism for immunomodulation and cancer chemotherapy[J]. Drug Discov Today, 2015, 20:609-617.
[84] Röhrig UF, Majjigapu SR, Vogel P, et al. Challenges in the discovery of indoleamine 2,3-dioxygenase 1(IDO1) inhibitors[J]. J Med Chem, 2015, 58:9421-9437.
[85] Zhang X, Sun XX, Xue D, et al. Conformation-dependent scFv antibodies specifically recognize the oligomers assembled from various amyloids and show colocalization of amyloid fibrils with oligomers in patients with amyloidoses[J]. BBA-Proteins Proteomics, 2011, 1814:1703-1712.
[86] Mautino MR, Jaipuri FA, Waldo J, et al. NLG919, a novel indoleamine-2,3-dioxygenase (IDO)-pathway inhibitor drug candidate for cancer therapy:Proceedings of the 104th Annual Meeting of the American Association for Cancer Research[C]. Washington:AACR, 2013:491.
[87] Nayak A, Hao Z, Sadek R, et al. A Phase I study of NLG919 for adult patients with recurrent advanced solid tumors[J]. J Immunother Cancer, 2014, 2(S3):P250.
[88] Siu LL. BMS-986205, an optimized indoleamine 2,3-dioxygenase 1(IDO1) inhibitor, is well tolerated with potent pharmacodynamic (PD) activity, alone and in combination with nivolumab (nivo) in advanced cancers in a phase 1/2A trial:Proceedings of the American Association for Cancer Research Annual Meeting[C]. National Harbor, 2017:1-5.
[89] Salter M, Hazelwood R, Pogson CI, et al. The effects of a novel and selective inhibitor of tryptophan 2,3-dioxygenase on tryptophan and serotonin metabolism in the rat[J]. Biochem Pharmacol, 1995, 49:1435-1442.
[90] Dolušić E, Larrieu P, Moineaux L, et al. Tryptophan 2,3-dioxygenase (TDO) inhibitors. 3-(2-(pyridyl) ethenyl) indoles as potential anticancer immunomodulators[J]. J Med Chem, 2011, 54:5320-5334.
[91] Bakmiwewa SM, Fatokun AA, Tran A, et al. Identification of selective inhibitors of indoleamine 2,3-dioxygenase 2[J]. Bioorg Med Chem Lett, 2012, 22:7641-7646.
[92] Aitken JB, Austin CJD, Hunt NH, et al. The Fe-heme structure of met-indoleamine 2,3-dioxygenase-2 determined by X-ray absorption fine structure[J]. Biochem Biophys Res Commun, 2014, 450:25-29.
[93] Löb S, Königsrainer A, Zieker D, et al. IDO1 and IDO2 are expressed in human tumors:levo-but not dextro-1-methyl tryptophan inhibits tryptophan catabolism[J]. Cancer Immunol Immunother, 2009, 58:153-157.
[94] Sørensen RB, Køllgaard T, Andersen RS, et al. Spontaneous cytotoxic T-cell reactivity against indoleamine 2,3-dioxygenase-2[J]. Cancer Res, 2011, 71:2038-2044.
[95] Zhang W, Ramamoorthy Y, Kilicarslan T, et al. Inhibition of cytochromes P450 by antifungal imidazole derivatives[J]. Drug Metab Dispos, 2002, 30:314-318.
[96] Röhrig UF, Majjigapu SR, Chambon M, et al. Detailed analysis and follow-up studies of a high-throughput screening for indoleamine 2,3-dioxygenase 1(IDO1) inhibitors[J]. Eur J Med Chem, 2014, 84:284-301.
[97] Daniele C, Saverio T, Ovidio B, et al. Expanding targets for a metabolic therapy of cancer:L-asparaginase[J]. Recent Patents Anti-Cancer Drug Discov, 2012, 7:4-13.
[98] Maggi M, Mittelman SD, Parmentier JH, et al. A protease-resistant Escherichia coli asparaginase with outstanding stability and enhanced anti-leukaemic activity in vitro[J]. Sci Rep, 2017, 7:14479.
[99] Phillips MM, Sheaff MT, Szlosarek PW. Targeting arginine-dependent cancers with arginine-degrading enzymes:opportunities and challenges[J]. Cancer Res Treat, 2013, 45:251-262.
[100] Sica A, Porta C, Morlacchi S, et al. Origin and functions of tumor-associated myeloid cells (TAMCs)[J]. Cancer Microenviron, 2012, 5:133-149.
[101] Geiger R, Rieckmann JC, Wolf T, et al. L-Arginine modulates T cell metabolism and enhances survival and anti-tumor activity[J]. Cell, 2016, 167:829-842.
[102] Fallarino F, Grohmann U, Vacca C, et al. T cell apoptosis by tryptophan catabolism[J]. Cell Death Differ, 2002, 9:1069-1077.
[103] Fallarino F, Grohmann U, You S, et al. The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor ζ-chain and induce a regulatory phenotype in naive T cells[J]. J Immunol, 2006, 176:6752-6761.
[104] Kung HN, Marks JR, Chi JT. Glutamine synthetase is a genetic determinant of cell type-specific glutamine independence in breast epithelia[J]. PLoS Genet, 2011, 7:e1002229.
[105] Souba WW. Glutamine and cancer[J]. Ann Surg, 1993, 218:715-728.
[106] Basun H, Forssell LG, Almkvist O, et al. Amino acid concentrations in cerebrospinal fluid and plasma in Alzheimer's disease and healthy control subjects[J]. J Neural Transm Park Dis Dement Sect, 1990, 2:295-304.
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