• 川北醫(yī)學(xué)院附屬醫(yī)院普外一科(四川南充 637000);

目的  探討吲哚胺2,3雙加氧酶(IDO)與胃癌免疫逃逸關(guān)系的研究現(xiàn)狀及發(fā)展趨勢。
方法  回顧性分析近10年來國內(nèi)、外有關(guān)IDO、胃癌免疫逃逸以及二者之間的關(guān)系的相關(guān)文獻(xiàn)。
結(jié)果  胃癌通過CD4+CD8+等調(diào)節(jié)性T細(xì)胞誘導(dǎo)樹突狀細(xì)胞IDO的表達(dá),使得其所處的微環(huán)境出現(xiàn)“色氨酸饑餓”,從而抑制T細(xì)胞增殖;同時(shí),色氨酸代謝產(chǎn)物對T細(xì)胞亦存在細(xì)胞毒性作用,抑制T細(xì)胞的增殖。IDO特異性抑制劑1-MT與化療藥物結(jié)合起來在胃癌的治療上有協(xié)同作用。
結(jié)論  IDO作為免疫調(diào)節(jié)酶可能在胃癌誘導(dǎo)機(jī)體產(chǎn)生免疫耐受過程中起著關(guān)鍵性作用,其可能成為抑制胃惡性腫瘤形成和提高腫瘤免疫治療效果的新靶點(diǎn)。

引用本文: 徐秀連,肖江衛(wèi),王崇樹. 吲哚胺2,3-雙加氧酶與胃癌免疫逃逸關(guān)系的研究進(jìn)展. 中國普外基礎(chǔ)與臨床雜志, 2012, 19(11): 1255-1259. doi: 復(fù)制

1. Munn DH, Mellor AL. Indoleamine 2,3-dioxygenase and tumor-induced tolerance[J]. J Clin Invest, 2007, 117(5):1147-1154.
2. ,3-dioxygenase in gastric cancer cells in vitro[J]. Mol MedReport, 2011, 4(1):169-173.
3. ,3-dioxygenase in dendritic cells by stereoisomers of 1-methyl-tryptophan correlates with antitumor responses[J]. Cancer Res, 2007, 67(2):792-801.
4. Clifton GT, Peoples GE. Overcoming cancer immune tolerance and escape[J]. Clin Cancer Res, 2009, 15(3):749-751.
5. Bronte V, Mocellin S. Suppressive influences in the immuneresponse to cancer[J]. J Immunother, 2009, 32(1):1-11.
6. Zindl CL, Chaplin DD. Immunology. Tumor immune evasion[J]. Science, 2010, 328(5979):697-698.
7. 王敏慧. 吲哚胺2,3-二氧化酶的生物學(xué)性質(zhì)及與疾病的關(guān)系[J]. 國外醫(yī)學(xué)臨床生物化學(xué)與檢驗(yàn)學(xué)分冊, 2000, 21(3):151-153.
8. Belladonna ML, Orabona C, Grohmann U, et al. TGF-beta and kynurenines as the key to infectious tolerance[J]. Trends Mol Med, 2009, 15(2):41-49.
9. Munn DH, Sharma MD, Hou D, et al. Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes[J]. J Clin Invest, 2004, 114(2):280-290.
10. Fallarino F, Vacca C, Orabona C, et al. Functional expression of indoleamine 2,3-dioxygenase by murine CD8 alpha (+) dendritic cells[J]. Int Immunol, 2002, 14(1):65-68.
11. Munn DH, Sharma MD, Lee JR, et al. Potential regulatory functionof human dendritic cells expressing indoleamine 2,3-dioxygenase[J]. Science, 2002, 297(5588):1867-1870.
12. Astigiano S, Morandi B, Costa R, et al. Eosinophil granulocytesaccount for indoleamine 2,3-dioxygenase-mediated immuneescape in human non-small cell lung Cancer[J]. Neoplasia, 2005, 7(4):390-396.
13. Löb S, Königsrainer A, Zieker D, et al. IDO1 and IDO2 are expressed in human tumors:levo- but not dextro-1-methyltryptophan inhibits tryptophan catabolism[J]. Cancer ImmunolImmunother, 2009, 58(1):153-157.
14. Uyttenhove C, Pilotte L, Théate I, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase[J]. Nat Med, 2003, 9(10):1269-1274.
15. Liu J, Lu G, Tang F, et al. Localization of indoleamine 2,3-dioxygenase in human esophageal squamous cell carcinomas[J]. Virchows Arch, 2009, 455(5):441-448.
16. Suzuki Y, Suda T, Furuhashi K, et al. Increased serum kynurenine/tryptophan ratio correlates with disease progression in lung cancer[J]. Lung Cancer, 2010, 67(3):361-365.
17. Brody JR, Costantino CL, Berger AC, et al. Expression ofindoleamine 2,3-dioxygenase in metastatic malignant melanoma recruits regulatory T cells to avoid immune detection and affects survival[J]. Cell Cycle, 2009, 8(12):1930-1934.
18. Weinlich G, Murr C, Richardsen L, et al. Decreased serum tryptophan concentration predicts poor prognosis in malignant melanoma patients[J]. Dermatology, 2007, 214(1):8-14.
19. Chamuleau ME, van de Loosdrecht AA, Hess CJ, et al. High INDO (indoleamine 2,3-dioxygenase) mRNA level in blasts of acute myeloid leukemic patients predicts poor clinical outcome[J]. Haematologica, 2008, 93(12):1894-1898.
20. 杜偉嬌, 于津浦, 李慧, 等. 腫瘤誘導(dǎo)的髓系來源抑制細(xì)胞中IDO表達(dá)相關(guān)機(jī)制研究[J]. 中國腫瘤臨床, 2011, 38(7):372-376.
21. 葉任高, 陸再英, 謝毅, 等. 內(nèi)科學(xué)[M]. 第6版. 北京:人民衛(wèi)生出版社, 2004:393-394.
22. 吳在德, 吳肇漢, 鄭樹, 等. 外科學(xué)[M]. 第6版. 北京:人民衛(wèi)生出版社, 2004:460.
23. Nagaraj S, Gupta K, Pisarev V, et al. Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer[J]. Nat Med, 2007, 13(7):828-835.
24. 王文軍, 李連宏, 張眾. 胃癌免疫逃疫機(jī)制的研究進(jìn)展[J]. 國外醫(yī)學(xué)腫瘤學(xué)分冊, 2005, 32(7):545-548.
25. Iero M, Valenti R, Huber V, et al. Tumour-released exosomes and their implications in cancer immunity[J]. Cell Death Differ, 2008, 15(1):80-88.
26. Munn DH. Indoleamine 2,3-dioxygenase, tumor-induced tolerance and counter-regulation[J]. Curr Opin Immunol, 2006, 18(2):220-225.
27. 李潤美, 魏楓, 于津浦, 等. Vav1在吲哚胺2,3雙加氧酶抑制T細(xì)胞中的作用初探[J]. 中國免疫學(xué)雜志, 2009, 25(9):786-791.
28. Kahler DJ, Mellor AL. T cell regulatory plasmacytoid dendritic cells expressing indoleamine 2,3 dioxygenase[J]. Handb Exp Pharmacol, 2009, (188):165-196.
29. Xu J, Yao N, Li YD. T-cell proliferation is inhibited by the induction of indoleamine 2,3-dioxygenase in spleen-derived dendritic cells in rat[J]. Chin Med J (Engl), 2011, 124(19):3154-3158.
30. Mellor AL, Munn DH. Tryptophan catabolism and regulation of adaptive immunity[J]. J Immunol, 2003, 170(12):5809-5813.
31. Xiao BG, Liu X, Link H. Antigen-specific T cell functions are suppressed over the estrogen-dendritic cell-indoleamine 2,3-dioxygenase axis[J]. Steroids, 2004, 69(10):653-659.
32. Mellor A. Indoleamine 2,3 dioxygenase and regulation of T cellimmunity[J]. Biochem Biophys Res Commun, 2005, 338(1):20-24.
33. Mellor AL, Munn DH. IDO expression by dendritic cells:tolerance and tryptophan catabolism[J]. Nat Rev Immunol, 2004, 4(10):762-774.
34. Le Rond S, Gonzalez A, Gonzalez AS, et al. Indoleamine 2,3 dioxygenase and human leucocyte antigen-G inhibit the T-cellalloproliferative response through two Independent pathways[J]. Immunology, 2005, 116(3):297-307.
35. Sas K, Robotka H, Toldi J, et al. Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders[J]. Neurol Sci, 2007, 257(1-2):221-239.
36. 戴向晨, 劉彤, 張樹建, 等. 吲哚胺2,3雙加氧酶對小鼠CD4+T細(xì)胞增殖的抑制作用[J]. 中華實(shí)驗(yàn)外科雜志, 2011, 28(9):1434-1437.
37. Ligam P, Manuelpillai U, Wallace EM, et al. Localisation of indoleamine 2,3-dioxygenase and kynurenine hydroxylase in the human placenta and decidua:implications for role of the kynurenine pathway in pregnancy[J]. Placenta, 2005, 26(6):498-504.
38. Löb S, Königsrainer A. Is IDO a key enzyme bridging the gapbetween tumor escape and tolerance induction?[J]. Langenbecks Arch Surg, 2008, 393(6):995-1003.
39. Hainz U, Jürgens B, Heitger A. The role of indoleamine 2,3-dioxygenase in transplantation[J]. Transpl Int, 2007, 20(2):118-127.
40. Onishi T, Ohishi Y, Imagawa K, et al. An assessment of theimmunological environment based on intratumoral cytokine production in renal cell carcinoma[J]. BJU Int, 1999, 83(4):488-492.
41. Mellor AL, Keskin DB, Johnson T, et al. Cells expressing indoleamine 2,3-dioxygenase inhibit T cell responses[J]. JImmunol, 2002, 168(8):3771-3776.
42. 龔非力. 醫(yī)學(xué)免疫學(xué)[M]. 第2版. 北京:科學(xué)出版社, 2004:152-153.
43. 安曉靜, 錢桂生, 王長征, 等. 吲哚胺2,3-雙加氧酶基因轉(zhuǎn)染未成熟樹突狀細(xì)胞對卵蛋白致敏小鼠模型CD4+T細(xì)胞的影響[J/OL]. 中華肺部疾病雜志(電子版), 2008, 1(2):143-147.
44. Fallarino F, Grohmann U, Hwang KW, et al. Modulation of tryptophan catabolism by regulatory T cells[J]. Nat Immunol, 2003, 4(12):1206-1212.
45. Martin-Fontecha A, Sebastiani S, Höpken UE, et al. Regulation of dendritic cell migration to the draining lymph node:impact on T lymphocyte traffic and priming[J]. J Exp Med, 2003, 198(4):615-621.
46. Wood KJ, Sawitzki B. Interferon gamma:a crucial role in the function of induced regulatory T cells in vivo[J]. Trends Immunol,.
47. Curti A, Pandolfi S, Valzasina B, et al. Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25-into CD25+T regulatory cells[J]. Blood, 2007, 109(7):2871-2877.
48. Liyanage UK, Moore TT, Joo HG, et al. Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma[J]. J Immunol, 2002, 169(5):2756-2761.
49. Grohmann U, Orabona C, Fallarino F, et al. CTLA-4-Ig regulates tryptophan catabolism in vivo[J]. Nat Immunol, 2002, 3(11):1097-1101.
50. Zhang R, Li H, Yu J, et al. Immunoactivative role of indoleamine.
51. Terness P, Chuang JJ, Bauer T, et al. Regulation of human autoandalloreactive T cells by indoleamine 2,3-dioxygenase (IDO)-producing dendritic cells:too much ado about IDO?[J]. Blood, 2005, 105(6):2480-2486.
52. 劉悅梅, 張玲, 張維東, 等. 胃癌組織吲哚胺2,3-雙加氧酶表達(dá)及其誘導(dǎo)腫瘤免疫逃逸的研究[J]. 中華腫瘤防治雜志, 2008, 15(15):1155-1158.
53. Hou DY, Muller AJ, Sharma MD, et al. Inhibition of indoleamine.
54. Löb S, Königsrainer A, Rammensee HG, et al. Inhibitors of indoleamine-2, 3-dioxygenase for cancer therapy:can we see the wood for the trees?[J]. Nat Rev Cancer, 2009, 9(6):445-452.
55. Muller AJ, Prendergast GC. Marrying immunotherapy with chemotherapy:why say IDO?[J]. Cancer Res, 2005, 65(18):8065-8068.
56. Gaspari P, Banerjee T, Malachowski WP, et al. Structure-activitystudy of brassinin derivatives as indoleamine 2,3-dioxygenaseinhibitors[J]. J Med Chem, 2006, 49(2):684-692.
57. Muller AJ, Duhadaway JB, Donover PS, et al. Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy[J]. Nat Med, 2005, 11(3):312-319.
58. , 27(4):183-187.
  1. 1. Munn DH, Mellor AL. Indoleamine 2,3-dioxygenase and tumor-induced tolerance[J]. J Clin Invest, 2007, 117(5):1147-1154.
  2. 2. ,3-dioxygenase in gastric cancer cells in vitro[J]. Mol MedReport, 2011, 4(1):169-173.
  3. 3. ,3-dioxygenase in dendritic cells by stereoisomers of 1-methyl-tryptophan correlates with antitumor responses[J]. Cancer Res, 2007, 67(2):792-801.
  4. 4. Clifton GT, Peoples GE. Overcoming cancer immune tolerance and escape[J]. Clin Cancer Res, 2009, 15(3):749-751.
  5. 5. Bronte V, Mocellin S. Suppressive influences in the immuneresponse to cancer[J]. J Immunother, 2009, 32(1):1-11.
  6. 6. Zindl CL, Chaplin DD. Immunology. Tumor immune evasion[J]. Science, 2010, 328(5979):697-698.
  7. 7. 王敏慧. 吲哚胺2,3-二氧化酶的生物學(xué)性質(zhì)及與疾病的關(guān)系[J]. 國外醫(yī)學(xué)臨床生物化學(xué)與檢驗(yàn)學(xué)分冊, 2000, 21(3):151-153.
  8. 8. Belladonna ML, Orabona C, Grohmann U, et al. TGF-beta and kynurenines as the key to infectious tolerance[J]. Trends Mol Med, 2009, 15(2):41-49.
  9. 9. Munn DH, Sharma MD, Hou D, et al. Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes[J]. J Clin Invest, 2004, 114(2):280-290.
  10. 10. Fallarino F, Vacca C, Orabona C, et al. Functional expression of indoleamine 2,3-dioxygenase by murine CD8 alpha (+) dendritic cells[J]. Int Immunol, 2002, 14(1):65-68.
  11. 11. Munn DH, Sharma MD, Lee JR, et al. Potential regulatory functionof human dendritic cells expressing indoleamine 2,3-dioxygenase[J]. Science, 2002, 297(5588):1867-1870.
  12. 12. Astigiano S, Morandi B, Costa R, et al. Eosinophil granulocytesaccount for indoleamine 2,3-dioxygenase-mediated immuneescape in human non-small cell lung Cancer[J]. Neoplasia, 2005, 7(4):390-396.
  13. 13. Löb S, Königsrainer A, Zieker D, et al. IDO1 and IDO2 are expressed in human tumors:levo- but not dextro-1-methyltryptophan inhibits tryptophan catabolism[J]. Cancer ImmunolImmunother, 2009, 58(1):153-157.
  14. 14. Uyttenhove C, Pilotte L, Théate I, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase[J]. Nat Med, 2003, 9(10):1269-1274.
  15. 15. Liu J, Lu G, Tang F, et al. Localization of indoleamine 2,3-dioxygenase in human esophageal squamous cell carcinomas[J]. Virchows Arch, 2009, 455(5):441-448.
  16. 16. Suzuki Y, Suda T, Furuhashi K, et al. Increased serum kynurenine/tryptophan ratio correlates with disease progression in lung cancer[J]. Lung Cancer, 2010, 67(3):361-365.
  17. 17. Brody JR, Costantino CL, Berger AC, et al. Expression ofindoleamine 2,3-dioxygenase in metastatic malignant melanoma recruits regulatory T cells to avoid immune detection and affects survival[J]. Cell Cycle, 2009, 8(12):1930-1934.
  18. 18. Weinlich G, Murr C, Richardsen L, et al. Decreased serum tryptophan concentration predicts poor prognosis in malignant melanoma patients[J]. Dermatology, 2007, 214(1):8-14.
  19. 19. Chamuleau ME, van de Loosdrecht AA, Hess CJ, et al. High INDO (indoleamine 2,3-dioxygenase) mRNA level in blasts of acute myeloid leukemic patients predicts poor clinical outcome[J]. Haematologica, 2008, 93(12):1894-1898.
  20. 20. 杜偉嬌, 于津浦, 李慧, 等. 腫瘤誘導(dǎo)的髓系來源抑制細(xì)胞中IDO表達(dá)相關(guān)機(jī)制研究[J]. 中國腫瘤臨床, 2011, 38(7):372-376.
  21. 21. 葉任高, 陸再英, 謝毅, 等. 內(nèi)科學(xué)[M]. 第6版. 北京:人民衛(wèi)生出版社, 2004:393-394.
  22. 22. 吳在德, 吳肇漢, 鄭樹, 等. 外科學(xué)[M]. 第6版. 北京:人民衛(wèi)生出版社, 2004:460.
  23. 23. Nagaraj S, Gupta K, Pisarev V, et al. Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer[J]. Nat Med, 2007, 13(7):828-835.
  24. 24. 王文軍, 李連宏, 張眾. 胃癌免疫逃疫機(jī)制的研究進(jìn)展[J]. 國外醫(yī)學(xué)腫瘤學(xué)分冊, 2005, 32(7):545-548.
  25. 25. Iero M, Valenti R, Huber V, et al. Tumour-released exosomes and their implications in cancer immunity[J]. Cell Death Differ, 2008, 15(1):80-88.
  26. 26. Munn DH. Indoleamine 2,3-dioxygenase, tumor-induced tolerance and counter-regulation[J]. Curr Opin Immunol, 2006, 18(2):220-225.
  27. 27. 李潤美, 魏楓, 于津浦, 等. Vav1在吲哚胺2,3雙加氧酶抑制T細(xì)胞中的作用初探[J]. 中國免疫學(xué)雜志, 2009, 25(9):786-791.
  28. 28. Kahler DJ, Mellor AL. T cell regulatory plasmacytoid dendritic cells expressing indoleamine 2,3 dioxygenase[J]. Handb Exp Pharmacol, 2009, (188):165-196.
  29. 29. Xu J, Yao N, Li YD. T-cell proliferation is inhibited by the induction of indoleamine 2,3-dioxygenase in spleen-derived dendritic cells in rat[J]. Chin Med J (Engl), 2011, 124(19):3154-3158.
  30. 30. Mellor AL, Munn DH. Tryptophan catabolism and regulation of adaptive immunity[J]. J Immunol, 2003, 170(12):5809-5813.
  31. 31. Xiao BG, Liu X, Link H. Antigen-specific T cell functions are suppressed over the estrogen-dendritic cell-indoleamine 2,3-dioxygenase axis[J]. Steroids, 2004, 69(10):653-659.
  32. 32. Mellor A. Indoleamine 2,3 dioxygenase and regulation of T cellimmunity[J]. Biochem Biophys Res Commun, 2005, 338(1):20-24.
  33. 33. Mellor AL, Munn DH. IDO expression by dendritic cells:tolerance and tryptophan catabolism[J]. Nat Rev Immunol, 2004, 4(10):762-774.
  34. 34. Le Rond S, Gonzalez A, Gonzalez AS, et al. Indoleamine 2,3 dioxygenase and human leucocyte antigen-G inhibit the T-cellalloproliferative response through two Independent pathways[J]. Immunology, 2005, 116(3):297-307.
  35. 35. Sas K, Robotka H, Toldi J, et al. Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders[J]. Neurol Sci, 2007, 257(1-2):221-239.
  36. 36. 戴向晨, 劉彤, 張樹建, 等. 吲哚胺2,3雙加氧酶對小鼠CD4+T細(xì)胞增殖的抑制作用[J]. 中華實(shí)驗(yàn)外科雜志, 2011, 28(9):1434-1437.
  37. 37. Ligam P, Manuelpillai U, Wallace EM, et al. Localisation of indoleamine 2,3-dioxygenase and kynurenine hydroxylase in the human placenta and decidua:implications for role of the kynurenine pathway in pregnancy[J]. Placenta, 2005, 26(6):498-504.
  38. 38. Löb S, Königsrainer A. Is IDO a key enzyme bridging the gapbetween tumor escape and tolerance induction?[J]. Langenbecks Arch Surg, 2008, 393(6):995-1003.
  39. 39. Hainz U, Jürgens B, Heitger A. The role of indoleamine 2,3-dioxygenase in transplantation[J]. Transpl Int, 2007, 20(2):118-127.
  40. 40. Onishi T, Ohishi Y, Imagawa K, et al. An assessment of theimmunological environment based on intratumoral cytokine production in renal cell carcinoma[J]. BJU Int, 1999, 83(4):488-492.
  41. 41. Mellor AL, Keskin DB, Johnson T, et al. Cells expressing indoleamine 2,3-dioxygenase inhibit T cell responses[J]. JImmunol, 2002, 168(8):3771-3776.
  42. 42. 龔非力. 醫(yī)學(xué)免疫學(xué)[M]. 第2版. 北京:科學(xué)出版社, 2004:152-153.
  43. 43. 安曉靜, 錢桂生, 王長征, 等. 吲哚胺2,3-雙加氧酶基因轉(zhuǎn)染未成熟樹突狀細(xì)胞對卵蛋白致敏小鼠模型CD4+T細(xì)胞的影響[J/OL]. 中華肺部疾病雜志(電子版), 2008, 1(2):143-147.
  44. 44. Fallarino F, Grohmann U, Hwang KW, et al. Modulation of tryptophan catabolism by regulatory T cells[J]. Nat Immunol, 2003, 4(12):1206-1212.
  45. 45. Martin-Fontecha A, Sebastiani S, Höpken UE, et al. Regulation of dendritic cell migration to the draining lymph node:impact on T lymphocyte traffic and priming[J]. J Exp Med, 2003, 198(4):615-621.
  46. 46. Wood KJ, Sawitzki B. Interferon gamma:a crucial role in the function of induced regulatory T cells in vivo[J]. Trends Immunol,.
  47. 47. Curti A, Pandolfi S, Valzasina B, et al. Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25-into CD25+T regulatory cells[J]. Blood, 2007, 109(7):2871-2877.
  48. 48. Liyanage UK, Moore TT, Joo HG, et al. Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma[J]. J Immunol, 2002, 169(5):2756-2761.
  49. 49. Grohmann U, Orabona C, Fallarino F, et al. CTLA-4-Ig regulates tryptophan catabolism in vivo[J]. Nat Immunol, 2002, 3(11):1097-1101.
  50. 50. Zhang R, Li H, Yu J, et al. Immunoactivative role of indoleamine.
  51. 51. Terness P, Chuang JJ, Bauer T, et al. Regulation of human autoandalloreactive T cells by indoleamine 2,3-dioxygenase (IDO)-producing dendritic cells:too much ado about IDO?[J]. Blood, 2005, 105(6):2480-2486.
  52. 52. 劉悅梅, 張玲, 張維東, 等. 胃癌組織吲哚胺2,3-雙加氧酶表達(dá)及其誘導(dǎo)腫瘤免疫逃逸的研究[J]. 中華腫瘤防治雜志, 2008, 15(15):1155-1158.
  53. 53. Hou DY, Muller AJ, Sharma MD, et al. Inhibition of indoleamine.
  54. 54. Löb S, Königsrainer A, Rammensee HG, et al. Inhibitors of indoleamine-2, 3-dioxygenase for cancer therapy:can we see the wood for the trees?[J]. Nat Rev Cancer, 2009, 9(6):445-452.
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