髓源性抑制细胞在胃癌患者外周血和肿瘤灶中的表达水平及临床意义
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摘要
胃癌患者外周血和肿瘤灶中髓源性抑制细胞的表达水平及临床意义
目的：探讨髓源性抑制细胞（MDSC）在胃癌患者外周血和肿瘤灶中的表达水平及临床意义。
方法：1选取胃癌患者36例和健康体检者10例，收集外周血标本，用流式细胞术检测外周血中以HLA-DR~-CD14~-CD33~+表达特征的PBWC为来源的MDSC表达水平；
2收集手术切除的同一胃癌患者癌组织（癌巢部位）标本（36例），用流式细胞仪检测以HLA-DR~-CD14~-CD33~+MDSC在肿瘤局部表达情况；
3结合患者生化指标，利用统计学软件，分析其与HLA-DR~-CD14~-CD33~+MDSC表达水平之间的关系；
4结合临床资料如，性别、年龄、肿瘤大小、淋巴结转移、远处转移、病理类型、分化程度和TNM临床分期等因素，利用统计学软件，分析HLA-DR~-CD14~-CD33~+MDSC在肿瘤进展以及预后中的作用；
5收集同一胃癌患者在术前、术后30天2个时间点的外周血标本（15例），检测HLA-DR~-CD14~-CD33~+MDSC表达水平，分析是否与肿瘤负荷呈动态相关。
结果：1．胃癌患者外周血中以HLA-DR~-CD14~-CD33~+MDSC表达水平显著高于正常人。
2．胃癌患者外周血中HLA-DR~-CD14~-CD33~+MDSC表达水平显著高于肿瘤组织；二者存在正相关关系。
3．胃癌患者外周血中HLA-DR~-CD14~-CD33~+MDSC表达水平与ALB,GGT,TT成负相关，与CRS成正相关。
4．浸润程度T3~4者MDSC表达水平高于T1~2者；有淋巴结转移者MDSC表达水平显著高于无淋巴结转移者；有远处转移者MDSC表达水平显著高于无远处转移者；Ⅲ、Ⅳ期者MDSC表达水平显著高于Ⅰ、Ⅱ期者。
5．胃癌患者术后30天外周血中MDSC表达水平低于术前，高于健康人。
结论：1．胃癌患者外周血和肿瘤灶中HLA-DR~-CD14~-CD33~+MDSC表达水平与肿瘤发生、发展密切相关。
2．胃癌术后外周血中MDSC表达水平有所下降，提示减轻肿瘤负荷后机体抗肿瘤免疫功能有所恢复。
3．外周血MDSC表达水平可作为胃癌患者临床监测的指标。
4．MDSC提供了胃癌免疫治疗的新方法。
Objective: To investigate the frequency and clinical significance of Myeloid-derivedsuppressor cells in peripheral blood and tumor foci of the patients with gastric cancer
Methods:1．The peripheral blood specimens of36gastric cancer patients and10healthy adults were collected in the Department of General Surgery of the First Affiliatedof Soochow University. Make the expression pattern of peripheral blood white cells(PBWC) in HLA-DR~-CD14~-CD33~+as monocyte derived MDSC. Flow cytometry was usedto detect and analyze the frequency and clinical significance of MDSC in peripheral bloodof two groups.
2．The tumor foci(tumor nest site) specimens which was operationed excision of36gastric cancer patients were collected. Flow cytometry was used to detect and analyze theexpression pattern of tumor foci in HLA-DR~-CD14~-CD33~+MDSC in tumor cases;
3．Analyse the relationship between the biochemical indicators of patients with gastriccancer patients and the proportion of HLA-DR~-CD14~-CD33~+MDSC.
4．Use statistical software to analysis the influence of HLA-DR~-CD14~-CD33~+MDSCin tumor progression and prognosis, combining with clinical data such as age, gender,tumor size, lymph node, metastasis, distant metastasis, histologic type, degree ofdifferentiation and TNM stages.
5．Collect the peripheral blood specimens(n=15) of gastric cancer patients at two timepoints(before postoperative and30days after operation),according to the above researchprogram and analysis the dynamic relationships between the proportion ofHLA-DR~-CD14~-CD33~+MDSC and tumor load.
Results:1．The proportion of HLA-DR~-CD14~-CD33~+MDSC in the peripheral bloodof gastric cancer patients is significantly higher than the healthy humans'.
2．The proportion of HLA-DR~-CD14~-CD33~+MDSC in the peripheral blood ofgastric cancer patients is significantly higher than the proportion of HLA-DR~-CD14~-CD33~+MDSC in The tumor foci(tumor nest site).They have positive relationship with theproportion of HLA-DR~-CD14~-CD33~+MDSC.
3．The proportion of HLA-DR~-CD14~-CD33~+MDSC in the peripheral blood ofgastric cancer patients has negative relationship with ALB, GGT, TT, and positiverelationship with CRS.
4．The proportion of T3and T4infiltration degree gastric cancer patients is higherthan the proportion of MDSC of T1and T2infiltration degree patients, the proportion ofMDSC with distant metastases is significantly higher than those without distant metastases,gastric cancer patients with lymph-node metastasis express much more MDSC than not,the proportion of MDSC of Ⅲ and Ⅳ period gastric cancer patients is significantly higherthan the proportion of Ⅰand Ⅱperiod patients.
5．The proportion of MDSC of gastric cancer patients decreased obviously at the30thday after operation, which is significantly higher than before the operation.
Conclusion:1．The proportion of HLA-DR~-CD14~-CD33~+MDSC in peripheral bloodof gastric cancer patients is related to the occurrence and progression of tumor.
2．The proportion of MDSC decreases after resection, which suggests that the immunefunction recovered in a certain extent.
3．The proportion of MDSC in peripheral blood may become a good cellularimmunological index of cancer patients in clinical monitor.
4．MDSC provides a new way of gastric cancer immunotherapy.
目的：探讨髓源性抑制细胞（MDSC）在胃癌患者外周血和肿瘤灶中的表达水平及临床意义。
方法：1选取胃癌患者36例和健康体检者10例，收集外周血标本，用流式细胞术检测外周血中以HLA-DR~-CD14~-CD33~+表达特征的PBWC为来源的MDSC表达水平；
2收集手术切除的同一胃癌患者癌组织（癌巢部位）标本（36例），用流式细胞仪检测以HLA-DR~-CD14~-CD33~+MDSC在肿瘤局部表达情况；
3结合患者生化指标，利用统计学软件，分析其与HLA-DR~-CD14~-CD33~+MDSC表达水平之间的关系；
4结合临床资料如，性别、年龄、肿瘤大小、淋巴结转移、远处转移、病理类型、分化程度和TNM临床分期等因素，利用统计学软件，分析HLA-DR~-CD14~-CD33~+MDSC在肿瘤进展以及预后中的作用；
5收集同一胃癌患者在术前、术后30天2个时间点的外周血标本（15例），检测HLA-DR~-CD14~-CD33~+MDSC表达水平，分析是否与肿瘤负荷呈动态相关。
结果：1．胃癌患者外周血中以HLA-DR~-CD14~-CD33~+MDSC表达水平显著高于正常人。
2．胃癌患者外周血中HLA-DR~-CD14~-CD33~+MDSC表达水平显著高于肿瘤组织；二者存在正相关关系。
3．胃癌患者外周血中HLA-DR~-CD14~-CD33~+MDSC表达水平与ALB,GGT,TT成负相关，与CRS成正相关。
4．浸润程度T3~4者MDSC表达水平高于T1~2者；有淋巴结转移者MDSC表达水平显著高于无淋巴结转移者；有远处转移者MDSC表达水平显著高于无远处转移者；Ⅲ、Ⅳ期者MDSC表达水平显著高于Ⅰ、Ⅱ期者。
5．胃癌患者术后30天外周血中MDSC表达水平低于术前，高于健康人。
结论：1．胃癌患者外周血和肿瘤灶中HLA-DR~-CD14~-CD33~+MDSC表达水平与肿瘤发生、发展密切相关。
2．胃癌术后外周血中MDSC表达水平有所下降，提示减轻肿瘤负荷后机体抗肿瘤免疫功能有所恢复。
3．外周血MDSC表达水平可作为胃癌患者临床监测的指标。
4．MDSC提供了胃癌免疫治疗的新方法。
Objective: To investigate the frequency and clinical significance of Myeloid-derivedsuppressor cells in peripheral blood and tumor foci of the patients with gastric cancer
Methods:1．The peripheral blood specimens of36gastric cancer patients and10healthy adults were collected in the Department of General Surgery of the First Affiliatedof Soochow University. Make the expression pattern of peripheral blood white cells(PBWC) in HLA-DR~-CD14~-CD33~+as monocyte derived MDSC. Flow cytometry was usedto detect and analyze the frequency and clinical significance of MDSC in peripheral bloodof two groups.
2．The tumor foci(tumor nest site) specimens which was operationed excision of36gastric cancer patients were collected. Flow cytometry was used to detect and analyze theexpression pattern of tumor foci in HLA-DR~-CD14~-CD33~+MDSC in tumor cases;
3．Analyse the relationship between the biochemical indicators of patients with gastriccancer patients and the proportion of HLA-DR~-CD14~-CD33~+MDSC.
4．Use statistical software to analysis the influence of HLA-DR~-CD14~-CD33~+MDSCin tumor progression and prognosis, combining with clinical data such as age, gender,tumor size, lymph node, metastasis, distant metastasis, histologic type, degree ofdifferentiation and TNM stages.
5．Collect the peripheral blood specimens(n=15) of gastric cancer patients at two timepoints(before postoperative and30days after operation),according to the above researchprogram and analysis the dynamic relationships between the proportion ofHLA-DR~-CD14~-CD33~+MDSC and tumor load.
Results:1．The proportion of HLA-DR~-CD14~-CD33~+MDSC in the peripheral bloodof gastric cancer patients is significantly higher than the healthy humans'.
2．The proportion of HLA-DR~-CD14~-CD33~+MDSC in the peripheral blood ofgastric cancer patients is significantly higher than the proportion of HLA-DR~-CD14~-CD33~+MDSC in The tumor foci(tumor nest site).They have positive relationship with theproportion of HLA-DR~-CD14~-CD33~+MDSC.
3．The proportion of HLA-DR~-CD14~-CD33~+MDSC in the peripheral blood ofgastric cancer patients has negative relationship with ALB, GGT, TT, and positiverelationship with CRS.
4．The proportion of T3and T4infiltration degree gastric cancer patients is higherthan the proportion of MDSC of T1and T2infiltration degree patients, the proportion ofMDSC with distant metastases is significantly higher than those without distant metastases,gastric cancer patients with lymph-node metastasis express much more MDSC than not,the proportion of MDSC of Ⅲ and Ⅳ period gastric cancer patients is significantly higherthan the proportion of Ⅰand Ⅱperiod patients.
5．The proportion of MDSC of gastric cancer patients decreased obviously at the30thday after operation, which is significantly higher than before the operation.
Conclusion:1．The proportion of HLA-DR~-CD14~-CD33~+MDSC in peripheral bloodof gastric cancer patients is related to the occurrence and progression of tumor.
2．The proportion of MDSC decreases after resection, which suggests that the immunefunction recovered in a certain extent.
3．The proportion of MDSC in peripheral blood may become a good cellularimmunological index of cancer patients in clinical monitor.
4．MDSC provides a new way of gastric cancer immunotherapy.
引文
[1]刘金龙，陈国玉，刘训良.关于胃癌手术发展的回顾与思考.医学与哲学.2001年22卷5期.35-37
[2]Gabrilovich DI, Bronte V, Chen SH, et al. The terminology issue for myeloid-derivedsuppressor cells [J]. Cancer Res,2007,67(1):425.
[3] Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of theimmune system. Nat Rev Immunol,2009,9(3):162174.
[4]Ilkovitch D, Lopez DM. The liver is a site for tumor-induced myeloid-derivedsuppressor cell accumulation and immunosuppression. Cancer Res,2009,69(13):55145521.
[5]Youn JI, Nagaraj S, Collazo M, et al. Subsets of myeloid-derived suppressor cells intumor-bearing mice [J]. J Immunol,2008,181(8):5791-5802.
[6]Hestdal K, Ruscetti FW, Ihle JN, et al. Characterization and regulation of RB6-8C5antigen expression on murine bone marrow cells [J]. J Immunol,1991,147(1):22-28.
[7]Movahedi K, Guilliams M, Van den Bossche J, et al. Identification of discretetumor-induced myeloid-derived suppressor cell subpopulations with distinct Tcell-suppressive activity [J]. Blood,2008,111(8):4233-4244.
[8]Dolcetti L, Marigo I, Mantelli B, et al. Myeloid-derived suppressor cell role intumor-related inflammation. Cancer Lett,2008,267:216225.
[9]Almand B, Clark JI, Nikitina E, et al. Increased production of immature myeloid cells incancer patients: a mechanism of immunosuppression in cancer [J]. J Immunol,2001,166(1):678-689.
[10]Sinha P, Okoro C, Foell D, et al. Proinflammatory S100proteins regulate theaccumulation of myeloid-derived suppressor cells. J Immunol,2008,181:4666-4675.
[1] GabrjloVich D，Bronte V，Chen SH，et a1．The terminolog issue on myeloid—derivedsuppressorcellsf[J]．Cancer Res，2007，67(1)：425-426。
[2] Ilkovitch D, Lopez DM. The liver is a site for tumor-induced myeloid-derivedsuppressor cell accumulation and immunosuppression. Cancer Res,2009,69:55145521.
[3] Serafini P, Borrello I, Bronte V. Myeloid suppressor cells in cancer: recruitment,phenotype properties, and mechanisms of immune suppression [J]. Semin Cancer Biol,2006,16(1):53-65.
[4] Ko JS, Bukowski RM, Fincke JH. Myeloid-derived suppressor cells: a noveltherapeutic target [J].Curr Oncol Rep,2009,11(2):87293.
[5] Almand B, Clark J I, Nikitina E,et al.Gabrilovich. Increased production of immaturemyeloid cells in cancer patients: a mechanism of immunosuppression in cancer [J].JImmunol,2001,166(1):6782689
[6] Roitt I, Broseoff J, Male D.周光炎译.免疫学[M].第6版.北京:人民卫生出版社,2002:301-302.
[7] Ostrand-Rosenberg S, Sinha P. Myeloid-derived suppressor cells: linking inflammationand cancer. J Immunol.2009,182:44994506.
[8] Sinha P, Okoro C, Foell D, et al. Proinflammatory S100proteins regulate theaccumulation of myeloid-derived suppressor cells. J Immunol,2008,181:46664675.
[9] Li Y, DeBusk LM, Fukuda K, et al. Expansion of myeloid immune suppressorGr+CD11b+cells in tumor-bearing host directly promotes tumor angiogenesis[J].Cancer Cell,2004,6(4):409-421.
[10] Diaz-Montero CM, Salem ML, Nishimura MI, et al. Increased circulatingmyeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumorburden, and doxorubicin-cyclophosphamide chemotherapy [J].Cancer ImmunolImmunother,2009,58(1):49-59.
[11] Bronte V， Zanovello P． Regulation of immune responses by L-argininemetabolism．Nat Rev Immuno1．2005；5：641-654．
[12] Serafini P，Borrello I，Bronte V．Myeloid suppressor cells in cancer：recruitment，phenotype, properties，and mechanisms of immune suppression．Semin CancerBiol．2006；16：53-65．
[13] Gabrilovich D I,Nagaraj S. Myeloid-derived suppressor cells as regulators of theimmune system[J].Nat Rev Immunol,2009,9(3):162-174.
[14] Schmielau J,Finn O J.Activated granulocytes and granulocyte-derived hydrogenperoxide are the underlying mechanism of suppression of T cell function in advancedcancer patients [J].Cancer Res,2001,61(12):4757-4760.
[15] Hildeman D A,Mitchell T,Aronow B,et al.Control of Bcl-2expression by reactiveoxygen species[J].Proc Natl Acad Sci USA,2003,100(25):15035-15040.
[16] Huang B,Pan P Y,Li Q,et al.Gr-1+CD115+immature myeloid suppressor cells mediatethe development of tumor-induced T cell anergy in tumor-bearing host[J].CancerRes,2006,66(2):1123-1131.
[17] Srivastava M K,Sinha P,Clements V K,et al. Myeloid-derived suppressor cells inhibitT cell activation by depleting cystine and cysteine [J].Cancer Res,2010,70(1),68-77.
[18] Lathers D, Clark J, Achille N, et al. Phase1B study to improve immune responses inhead and neck cancer patients using escalating doses of25-hydroxyvitamin D3[J].Cancer Immunol Immunother,2004,53(5):422-430.
[19] Pan P,Wang G,Yin B,et al.Reversion of immune tolerance in advanced malignancy:modulation of myeloid-derived suppressor cell development by blockade of stem-cellfactor function [J].Blood,2008,111(1):219-228.
[20] Serafini P, Meckel K, KelsoM, et al. Phosphodiesterase-5inhibition augmentsendogenous antitumor immunity by reducing myeloid-derived suppressor cellfunction [J]. J Exp Med,2006,203(12):2691-22702.
[21] Suzuki E, Kapoor V,Jassar AS,et al.Gemcitabine selectively eliminates splenicGr21+/CD11b+myeloid suppressor cells in tumor-bearing animals and enhancesantitumor immune activity[J]. Clin Cancer Res,2005,11(18):6713-6721.
[1]GabrjloVich D，Bronte V，Chen SH，et a1．The terminolog issue on myeloid—derivedsuppressorcellsf[J]．Cancer Res，2007，67(1)：425-426。
[2] Ko JS, Bukowski RM, Fincke JH. Myeloid-derived suppressor cells: a noveltherapeutic target [J]. Curr Oncol Rep,2009,11(2):87293.
[3] Almand B, Clark J I, Nikitina E, et al. Gabrilovich. Increased production of immaturemyeloid cells in cancer patients: a mechanism of immunosuppression in cancer [J]. JImmunol,2001,166(1):6782689
[4]Dolcetti L，Marigo I，Mantelli B．et a1．myeloid-derived suppressor cell role intumor-relatied inflammation．Cancer Lett，2008，267(2)：216-225．
[5]Ko JS，Zea AH，Rini BI，et a1.Sunitinib mediates reversal of myeloid-derivedsuppressor cell accumulation in renal cell carcinoma patients．Clin Cancer Res，2009，15(6)：2148-2157．
[6]Diaz-Montero CM， Salem ML, Nishimura MI, et al. Increased circulatingmyeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumorburden, and doxorubicin-cyclophosphamide chemotherapy. Cancer ImmunolImmunother,2009，58(1)：49-59．
[7]Kusmartsev S， Su Z， Heiser A， et a1． Reversal of myeloid cell-mediatedimmunosuppression in patients with metastatic renal cell carcinoma. Clin CancerRes,2008,14(24):8208-8278.
[8]Liu Y，Van Ginderachter JA, Brys L，ct a1．Nitric oxide-independent CTL suppressionduring tumor progression：association with arginase-producing(M2)myeloid cells．JImmuno1．2003；170：5064-5073．
[9]Salvadori S，Martinelli G, Zier K et a1．Resection of solid tumors reverses T cell defectsand restores protective immunity．J Immuno1．2000；164：2214-2220．
[10]Sinha P，Clements VK Ostrand-Rosenberg S，et a1．Reduction of myeloid-derivedsuppressor cells and induction of M1macrophages facilitate the rejection ofestablished meta static disease。J Immuno1．2005；174：636--645．
[11]Bronte V， Zanovello P． Regulation of immune responses by L-argininemetabolism．Nat Rev Immuno1．2005；5：641—654．
[12]Serafini P，Borrello I，Bronte V．Myeloid suppressor cells in cancer：recruitment，phenotype, properties，and mechanisms of immune suppression．Semin CancerBiol．2006；16：53-65．
[13] Pan PY, Wang GX, Yin B, et al. Reversion of immune tolerance in advancedmalignancy: modulation of myeloid-derived suppressor cell development by blockadeof stem-cell factor function [J].Blood,2008,111(1):219-228.
[14] Sinha P, Clements VK, Fulton AM, et al. Prostagland in E2promotes tumorprogression by inducing myeloid-derived suppressor cells [J]. Cancer Res,2007,67(9):4507-4513.
[15] Serafini P, Carbley R, Noonan KA, et al. High-dose GM-CSF-producing vaccinesimpair the immune response through the recruitment of myeloid suppressor cells [J].Cancer Res,2004,64(17):6337-6343.
[16] Gabrilovich D, Ishida T, Oyama T, et al. Vascular endothelial growth factor inhibitsthe development of dendritic cells and dramatically affects the differentiation ofmultiple hematopoietic lineages in vivo [J]. Blood,1998,92(11):4150-4166.
[17] Zhang Y, Liu Q, Zhang M, et al. Fas signal promotes lung cancer growth by recruitingmyeloid-derived suppressor cells via cancer cell-derived PGE2[J]. JImmunol,2009,182(6):3801-3808.
[18] Delano MJ, Scumpia PO, Weinstein JS, et al. MyD88-dependent expansion of animmature GR-1+CD11b+population induces T cell suppression and Th2polarization in sep sis [J]. J Exp Med,2007,204(6):1463-1474.
[19]Gabrilovich D I, Nagaraj S. Myeloid-derived suppressor cells as regulators of theimmune system[J].Nat Rev Immunol,2009,9(3):162-174.
[20]Schmielau J,Finn O J.Activated granulocytes and granulocyte-derived hydrogenperoxide are the underlying mechanism of suppression of T cell function in advancedcancer patients [J].Cancer Res,2001,61(12):4757-4760.
[21]Hildeman D A,Mitchell T,Aronow B,et al.Control of Bcl-2expression by reactiveoxygen species[J].Proc Natl Acad Sci USA,2003,100(25):15035-15040.
[22]Huang B,Pan P Y,Li Q,et al.Gr-1+CD115+immature myeloid suppressor cells mediatethe development of tumor-induced T cell anergy in tumor-bearing host[J].CancerRes,2006,66(2):1123-1131.
[23]Srivastava M K,Sinha P,Clements V K,et al. Myeloid-derived suppressor cells inhibitT cell activation by depleting cystine and cysteine [J].Cancer Res,2010,70(1),68-77.
[24]Hanson E M,Clements V K,Sinha P,et al. Myeloid-derived suppressor cellsdown-regulate L-selectin expression on CD4+and CD8+T cells[J].JImmunol,2009,183(2):937-944.
[25]Lathers D, Clark J, Achille N, et al. Phase1B study to improve immune responses inhead and neck cancer patients using escalating doses of25-hydroxyvitamin D3[J].Cancer Immunol Immunother,2004,53(5):422-430.
[26]Pan P,Wang G,Yin B,et al.Reversion of immune tolerance in advanced malignancy:modulation of myeloid-derived suppressor cell development by blockade of stem-cellfactor function [J].Blood,2008,111(1):219-228.
[27] Serafini P, Meckel K, KelsoM, et al. Phosphodiesterase-5inhibition augmentsendogenous antitumor immunity by reducing myeloid-derived suppressor cellfunction [J].J Exp Med,2006,203(12):2691-22702.
[28]Suzuki E, Kapoor V, Jassar AS, et al. Gemcitabine selectively eliminates splenicGr21+/CD11b+myeloid suppressor cells in tumor-bearing animals and enhancesantitumor immune activity[J]. Clin Cancer Res,2005,11(18):6713-6721.
[2]Gabrilovich DI, Bronte V, Chen SH, et al. The terminology issue for myeloid-derivedsuppressor cells [J]. Cancer Res,2007,67(1):425.
[3] Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of theimmune system. Nat Rev Immunol,2009,9(3):162174.
[4]Ilkovitch D, Lopez DM. The liver is a site for tumor-induced myeloid-derivedsuppressor cell accumulation and immunosuppression. Cancer Res,2009,69(13):55145521.
[5]Youn JI, Nagaraj S, Collazo M, et al. Subsets of myeloid-derived suppressor cells intumor-bearing mice [J]. J Immunol,2008,181(8):5791-5802.
[6]Hestdal K, Ruscetti FW, Ihle JN, et al. Characterization and regulation of RB6-8C5antigen expression on murine bone marrow cells [J]. J Immunol,1991,147(1):22-28.
[7]Movahedi K, Guilliams M, Van den Bossche J, et al. Identification of discretetumor-induced myeloid-derived suppressor cell subpopulations with distinct Tcell-suppressive activity [J]. Blood,2008,111(8):4233-4244.
[8]Dolcetti L, Marigo I, Mantelli B, et al. Myeloid-derived suppressor cell role intumor-related inflammation. Cancer Lett,2008,267:216225.
[9]Almand B, Clark JI, Nikitina E, et al. Increased production of immature myeloid cells incancer patients: a mechanism of immunosuppression in cancer [J]. J Immunol,2001,166(1):678-689.
[10]Sinha P, Okoro C, Foell D, et al. Proinflammatory S100proteins regulate theaccumulation of myeloid-derived suppressor cells. J Immunol,2008,181:4666-4675.
[1] GabrjloVich D，Bronte V，Chen SH，et a1．The terminolog issue on myeloid—derivedsuppressorcellsf[J]．Cancer Res，2007，67(1)：425-426。
[2] Ilkovitch D, Lopez DM. The liver is a site for tumor-induced myeloid-derivedsuppressor cell accumulation and immunosuppression. Cancer Res,2009,69:55145521.
[3] Serafini P, Borrello I, Bronte V. Myeloid suppressor cells in cancer: recruitment,phenotype properties, and mechanisms of immune suppression [J]. Semin Cancer Biol,2006,16(1):53-65.
[4] Ko JS, Bukowski RM, Fincke JH. Myeloid-derived suppressor cells: a noveltherapeutic target [J].Curr Oncol Rep,2009,11(2):87293.
[5] Almand B, Clark J I, Nikitina E,et al.Gabrilovich. Increased production of immaturemyeloid cells in cancer patients: a mechanism of immunosuppression in cancer [J].JImmunol,2001,166(1):6782689
[6] Roitt I, Broseoff J, Male D.周光炎译.免疫学[M].第6版.北京:人民卫生出版社,2002:301-302.
[7] Ostrand-Rosenberg S, Sinha P. Myeloid-derived suppressor cells: linking inflammationand cancer. J Immunol.2009,182:44994506.
[8] Sinha P, Okoro C, Foell D, et al. Proinflammatory S100proteins regulate theaccumulation of myeloid-derived suppressor cells. J Immunol,2008,181:46664675.
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