Study of Relationship of Indoleamine 2，3-Dioxygenase to Immune Escape of Gastric Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

XU Xiulian , XIAO Jiangwei , WANG Chongshu

The First Department of General Surgery， Affiliated Hospital of North Sichuan Medical College， Nanchong 637000， Sichuan Province， China;

Corresponding author：

Keywords：

Gastric cancer; Indoleamine 2，3-dioxygenase; Immune escape; Immune therapy

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective 　To explore the research status and development tendency of relation between indoleamine 2，3-dioxygenase （IDO） and immune escape of gastric cancer.
Methods 　The related literatures about IDO， immune escape of gastric cancer， and their the relationship at domestic and international in recent ten years were collected and reviewed.
Results 　Gastric cancers induced that dendritic cells expressed IDO by the CD4＋ CD8＋ regulatory T cells， which made the microenviroment tryptophan starvation， thus inhibited T cell proliferation. While tryptophan metabolites existed T cell cytotoxicity that inhibited T cell proliferation. IDO-specific inhibitor 1-MT combinated with chemotherapy drugs in the treatment for gastric cancer was a synergistic effect.
Conclusions 　IDO as an immune modulating enzymes may play a key role in the process of immune tolerance that induced by gastric body. IDO may become a new target for inhibition of gastric malignancy formation and enhance the effectiveness of tumor immune treatment.

Citation： XU Xiulian,XIAO Jiangwei,WANG Chongshu,.. Study of Relationship of Indoleamine 2，3-Dioxygenase to Immune Escape of Gastric Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2012, 19(11): 1255-1259. doi: Copy

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学性质及与疾病的关系[J]. 国外医学临床生物化学与检验学分册， 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.	杜伟娇，于津浦，李慧，等. 肿瘤诱导的髓系来源抑制细胞中IDO表达相关机制研究[J]. 中国肿瘤临床， 2011， 38(7)：372-376.
21.	叶任高，陆再英，谢毅，等. 内科学[M]. 第6版. 北京：人民卫生出版社， 2004：393-394.
22.	吴在德，吴肇汉，郑树，等. 外科学[M]. 第6版. 北京：人民卫生出版社， 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.	王文军，李连宏，张众. 胃癌免疫逃疫机制的研究进展[J]. 国外医学肿瘤学分册， 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.	李润美，魏枫，于津浦，等. Vav1在吲哚胺2，3双加氧酶抑制T细胞中的作用初探[J]. 中国免疫学杂志， 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，刘彤，张树建，等. 吲哚胺2，3双加氧酶对小鼠CD4＋T细胞增殖的抑制作用[J]. 中华实验外科杂志， 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.	龚非力. 医学免疫学[M]. 第2版. 北京：科学出版社， 2004：152-153.
43.	安晓静，钱桂生，王长征，等. 吲哚胺2，3-双加氧酶基因转染未成熟树突状细胞对卵蛋白致敏小鼠模型CD4＋T细胞的影响[J/OL]. 中华肺部疾病杂志(电子版)， 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.	刘悦梅，张玲，张维东，等. 胃癌组织吲哚胺2，3-双加氧酶表达及其诱导肿瘤免疫逃逸的研究[J]. 中华肿瘤防治杂志， 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. 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学性质及与疾病的关系[J]. 国外医学临床生物化学与检验学分册， 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. 杜伟娇，于津浦，李慧，等. 肿瘤诱导的髓系来源抑制细胞中IDO表达相关机制研究[J]. 中国肿瘤临床， 2011， 38(7)：372-376.
21. 叶任高，陆再英，谢毅，等. 内科学[M]. 第6版. 北京：人民卫生出版社， 2004：393-394.
22. 吴在德，吴肇汉，郑树，等. 外科学[M]. 第6版. 北京：人民卫生出版社， 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. 王文军，李连宏，张众. 胃癌免疫逃疫机制的研究进展[J]. 国外医学肿瘤学分册， 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. 李润美，魏枫，于津浦，等. Vav1在吲哚胺2，3双加氧酶抑制T细胞中的作用初探[J]. 中国免疫学杂志， 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，刘彤，张树建，等. 吲哚胺2，3双加氧酶对小鼠CD4＋T细胞增殖的抑制作用[J]. 中华实验外科杂志， 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. 龚非力. 医学免疫学[M]. 第2版. 北京：科学出版社， 2004：152-153.
43. 安晓静，钱桂生，王长征，等. 吲哚胺2，3-双加氧酶基因转染未成熟树突状细胞对卵蛋白致敏小鼠模型CD4＋T细胞的影响[J/OL]. 中华肺部疾病杂志(电子版)， 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. 刘悦梅，张玲，张维东，等. 胃癌组织吲哚胺2，3-双加氧酶表达及其诱导肿瘤免疫逃逸的研究[J]. 中华肿瘤防治杂志， 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.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Study of Relationship of Indoleamine 2，3-Dioxygenase to Immune Escape of Gastric Cancer

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