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蛋白质与多肽药物所重点实验室

秦志海(客座) 博士 研究员 博士生导师

国家973项目首席科学家 中科院生物物理所,中科院感染与免疫重点实验室,研究组长

研究方向:肿瘤微环境与肿瘤免疫

电子邮件:zhihai@ibp.ac.cn

电 话:010-64888570

通讯地址:北京市朝阳区大屯路15号(100101)

英文版个人网页:http://english.ibp.cas.cn/en_sourcedb_ibp/rck/EN_xsszmQ_V/202005/t20200519_341386.html

简 历:

  1987 - 1992 柏林自由大学免疫所,获医学博士学位

  1992 - 1994 美国Fox Chase癌症研究中心,博士后

  1994 - 2000 德国MDC分子医学中心,课题组长

  2000 - 2005 柏林自由大学,终生研究员,于2005年辞职

  2005 - 至今 中国科学院生物物理研究所,研究员

获奖及荣誉:

  1. 1998年获得国家杰出青年 B类基金(依托单位:上海第二军医大学)

  2. 2001年获柏林自由大学最佳科研奖

  CD4+ T cell-mediated tumor rejection involves inhibition of angiogenesis that is dependent on IFN?-receptor expression by non-hematopoietic cells

  3. 2007年北京市科技进步三等奖

社会任职:

  1. Journal of Immunology Research and Therapy 编委

  2. Cell Biochemistry & Function 编委

  3. Emerging Microbes and Infections 编委

  4. Cell Mol Immunol编委 (1999 - 2005)

  5. 中国癌症研究杂志(英文版) 编委

  6. 中国免疫学杂志 编委

  7. 免疫学杂志 编委

  8. 中国肿瘤生物治疗杂志 编委

  9. 中国免疫学会,肿瘤免疫与生物治疗分会 常务委员

(曾)任职情况:

  曾任中科院生物物理研究所学术委员会副主任

  曾任中科院生物物理研究所感染免疫中心主任

国际会议特邀报告(最近5年):

  1. 2012年冷泉港亚洲/国际肿瘤微环境协会联合会议 大会报告

  2. 2012年细胞治疗技术研讨会特邀报告

  3. 2013年芝加哥大学(北京)外科研讨会议 特邀报告

  4. 2013年医学与生物医学德国校友会议 特邀报告

  5. 2013年第14届国际TNF大会特邀报告

  6. 2013年冷泉港亚洲/国际肿瘤微环境协会联合会议 大会报告

  7. 2014年第九届免疫学大会分会主席

  8. 2014年淋巴管与血管基础及转化研究---2014苏州国际研讨会分会主席

  9. 2015年肿瘤与免疫治疗研讨会 特邀报告

  10. 2015年北京国际肿瘤微环境大会 特邀报告

  11. 2015年第十四届全国肿瘤生物治疗大会 特邀报告

  12. 2015年巴黎11届脑血管生物学国际大会 特邀报告

  13. 2015年第四届中日韩免疫学会议

  14. 2015年成都中德免疫学会议

  15. 2016年上海淋巴管系统与相关疾病学术研讨会会议日程

  16. 2016年郑州国际转化医学研讨会

  17. 2016年德累斯顿中德免疫学研讨会暨第二届中德肿瘤免疫学会议

研究方向:

  致力于研究炎症性细胞因子,如IFN,TNF,IL4等在肿瘤发生、发展及排斥过程中的作用,尤其是对肿瘤微环境形成和肿瘤间质细胞功能的影响。近年来,重点研究肿瘤免疫负调控肿瘤与相关成纤维细胞。

主要成果如下:

1. IFN抗血管生成效应是肿瘤免疫排斥的主要机制:

  本人长期研究发现,免疫效应机制除杀伤外,IFN依赖的抗血管新生是肿瘤免疫排斥的主要机制(Immunity,2000);进一步工作证明,IFN?作用于成纤维细胞抑制其产生VEGF,进而抑制血管内皮细胞和肿瘤的生长(J Immunol, 2007,J Immunol, 2009,J Pathol,2014);目前,在继续关注IFN对血管周细胞的作用。这项研究曾经获得北京市科技奖。

2. 细胞因子在炎-癌转变中的作用:

  研究发现在荷瘤小鼠和肿瘤病人中,伴随着肿瘤的生长,一群有免疫抑制功能的巨噬细胞(MDSC)在肿瘤、脾脏等部位聚集。本课题组首次发现多种异物,包括弗氏佐剂能够诱导MDSC产生(J Immunother, 2010);TNF可以通过TNFR-2促进MDSC的存活(J Clin Invest, 2012);而IFN通过IL17介导的炎症反应也能促进MDSC聚集和肿瘤发生(Cancer Research, 2009); 另外,IFN还通过抑制脂类代谢物LXA4合成,维持慢性炎症和肿瘤生长(Cancer Research, 2013)。而外源性IL4,或一些植物多糖在肿瘤生长早期能通过促进MDSC分化改变它们对肿瘤免疫的抑制作用(Gene therapy, 2010,Plos One,2012)。

3. 肿瘤免疫监视的存在方式:

  对于大多数非感染性炎症导致的肿瘤,传统的肿瘤免疫监视和免疫杀伤机制尚缺乏证据(Nature Immunol, 2004)。本人以化学物致癌为模型对肿瘤免疫机制进行了长期研究:发现机体对一些致癌物产生的组织修复(异物反应)过程是另一种免疫监视机制。IFN通过促进异物反应,抑制肿瘤发生(J Exp Med,2002);消除包裹在致癌物周围的成纤维细胞,导致肿瘤生发类型改变(Cancer Research,2013);另外,成纤维细胞针对异物能分泌MCP-1招募巨噬细胞,加速炎症反应,促进肿瘤形成(Am J Pathol, 2011)。

承担项目情况:

  1. 国家自然科学基金重大项目,化学物致癌过程中无菌性炎症分子网络的形成与调控,2013.1-2016.12,项目负责人

  2. 国家自然科学基金重点项目,成纤维细胞对炎症与肿瘤发生的调节作用和机制研究,2011.1-2014.12,项目负责人

  3. 国家重点基础研究发展计划(973 计划),炎症因子网络的免疫负调控作用和机制, 2012.1-2016.12,首席科学家

  4. 国家重点基础研究发展计划(973 计划),细胞因子在感染免疫病理中的作用机制研究,2006.1-2010.12,子课题负责人

  5. 科技部“863计划”,T细胞过继转移治疗胃肠道肿瘤新方法的应用研究,2007.1-2009.12,项目负责人

代表论著:

1. Xue, R*., Sheng, Y., Duan, X., Yang, Y., Ma, S., Xu, J., Wei, N., Shang, X., Li, F., Wan, J. andQin, Z*. (2020), Tie2‐expressing monocytes as a novel angiogenesis‐related cellular biomarker for non‐small cell lung cancer.Int. J. Cancer.

2. Li Y, Wang J, Song K, Liu S, Zhang H, Wang F, Ni C, Zhai W, Liang J,Qin Z*, Zhang J*. S100A4 promotes hepatocellular carcinogenesis by intensifying fibrosis-associated cancer cell stemness.Oncoimmunology. 2020 Feb 14;9(1):1725355.

3. Jiang H, Zhang L, Liu X, Sun W, Kato K, Chen C, Li X, Li T, Sun Z, Han W, Zhang F, Xiao Q, Yang Z, Hu J,Qin Z, Adams RH, Gao X, He Y*. Angiocrine FSTL1 (Follistatin-Like Protein 1) Insufficiency Leads to Atrial and Venous Wall Fibrosis via SMAD3 Activation.Arterioscler Thromb Vasc Biol. 2020 Apr;40(4):958-972.

4. Winkler L, Blasig R, Breitkreuz-Korff O, Berndt P, Dithmer S, Helms HC, Puchkov D, Devraj K, Kaya M,Qin Z, Liebner S, Wolburg H, Andjelkovic AV, Rex A, Blasig IE, Haseloff RF*. Tight junctions in the blood-brain barrier promote edema formation and infarct size in stroke - Ambivalent effects of sealing proteins.J Cereb Blood Flow Metab. 2020 Feb 13:271678X20904687.

5. Wu H, Han Y, Rodriguez Sillke Y, Deng H, Siddiqui S, Treese C, Schmidt F, Friedrich M, Keye J, Wan J, Qin Y, Kühl AA,Qin Z*, Siegmund B, Glauben R*. Lipid droplet-dependent fatty acid metabolism controls the immune suppressive phenotype of tumor-associated macrophages.EMBO Mol Med. 2019 Nov 7;11(11):e10698.

6. Deng L, Feng Z, Deng H*, Jiang Y, Song K, Shi Y, Liu S, Zhang J, Bai S,Qin Z*, Dong A*. Rational Design of Nanoparticles to Overcome Poor Tumor Penetration and Hypoxia-Induced Chemotherapy Resistance: Combination of Optimizing Size and Self-Inducing High Level of Reactive Oxygen Species.ACS Appl Mater Interfaces. 2019 Sep 4;11(35):31743-31754.

7. Zhang L, Qi Y, Min H, Ni C, Wang F, Wang B, Qin H, Zhang Y, Liu G, Qin Y, Duan X, Li F, Han X, Tao N, Zhang L,Qin Z*, Zhao Y*, Nie G*. Cooperatively Responsive Peptide Nanotherapeutic that Regulates Angiopoietin Receptor Tie2 Activity in Tumor Microenvironment To Prevent Breast Tumor Relapse after Chemotherapy.ACS Nano. 2019 May 28;13(5):5091-5102.

8. Ji T, Lang J, Ning B, Qi F, Wang H, Zhang Y, Zhao R, Yang X, Zhang L, Li W, Shi X,Qin Z*, Zhao Y*, Nie G*. Enhanced Natural Killer Cell Immunotherapy by Rationally Assembling Fc Fragments of Antibodies onto Tumor Membranes.Adv Mater. 2019 Feb;31(6):e1804395.

9. Ni C, Ma P, Wang R, Lou X, Liu X, Qin Y, Xue R, Blasig I, Erben U,Qin Z*. Doxorubicin-induced cardiotoxicity involves IFNγ-mediated metabolic reprogramming in cardiomyocytes.J Pathol. 2019 Mar;247(3):320-332.

10. Zhang J, Hou S, Gu J, Tian T, Yuan Q, Jia J,Qin Z, Chen Z. S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis.Oncoimmunology. 2018 Jun 11;7(8):e1461301.

11. Li Y, Bao J, Bian Y, Erben U, Wang P, Song K, Liu S, Li Z, Gao Z,Qin Z*. S100A4+ Macrophages Are Necessary for Pulmonary Fibrosis by Activating Lung Fibroblasts.Front Immunol. 2018 Aug 6;9:1776.

12. Sheng Y, Li F,Qin Z*. TNF Receptor 2 Makes Tumor Necrosis Factor a Friend of Tumors.Front Immunol. 2018 May 28;9:1170.

13. Zhang J, Song K, Wang J, Li Y, Liu S, Dai C, Chen L, Wang S,Qin Z*. S100A4 blockage alleviates agonistic anti-CD137 antibody-induced liver pathology without disruption of antitumor immunity.Oncoimmunology. 2018 Jan 23;7(4):e1296996.

14. Li Q, Dai C, Xue R, Wang P, Chen L, Han Y, Erben U,Qin Z*. S100A4 Protects Myeloid-Derived Suppressor Cells from Intrinsic Apoptosis via TLR4-ERK1/2 Signaling.Front Immunol. 2018 Mar 5;9:388.

15. Deng H, Song K, Zhang J, Deng L, Dong A*,Qin Z*. Modulating the rigidity of nanoparticles for tumor penetration.Chem Commun (Camb). 2018 Mar 25;54(24):3014-3017.

16. Hou S, Tian T, Qi D, Sun K, Yuan Q, Wang Z,Qin Z, Wu Z, Chen Z*, Zhang J*. S100A4 promotes lung tumor development through β-catenin pathway-mediated autophagy inhibition.Cell Death Dis. 2018 Feb 15;9(3):277.

17. Liu J, Kang SG, Wang P, Wang Y, Lv X, Liu Y, Wang F, Gu Z, Yang Z, Weber JK, Tao N,Qin Z, Miao Q, Chen C, Zhou R, Zhao Y. Molecular mechanism of Gd@C82(OH)22 increasing collagen expression: Implication for encaging tumor.Biomaterials. 2018 Jan;152:24-36. doi: 10.1016/j.biomaterials.2017.10.027. Epub 2017 Oct 16. PMID: 29080421.

18. Ji T, Lang J, Wang J, Cai R, Zhang Y, Qi F, Zhang L, Zhao X, Wu W, Hao J,Qin Z*, Zhao Y*, Nie G*. 2017. Designing Liposomes To Suppress Extracellular Matrix Expression To Enhance Drug Penetration and Pancreatic Tumor Therapy.ACS Nano, 11(9):8668-8678.

19. Ni C, Ma P, Qu L, Wu F, Hao J, Wang R, Lu Y, Yang W, Erben U,Qin Z*. 2017. Accelerated tumour metastasis due to interferon-gamma receptor-mediated dissociation of perivascular cells from blood vessels.J Pathol, 242(3):334-346.

20. Deng H, Song K, Zhao X, Li Y, Wang F, Zhang J, Dong A,Qin Z*. 2017. Tumor Microenvironment Activated Membrane Fusogenic Liposome with Speedy Antibody and Doxorubicin Delivery for Synergistic Treatment of Metastatic Tumors.ACS Appl Mater Interfaces, 9(11):9315-9326.

21. Xu X, Meng Q, Erben U, Wang P, Glauben R, Kuhl AA, Wu H, Ma CW, Hu M, Wang Y, Sun W, Jia J, Wu X, Chen W, Siegmund B,Qin Z*. 2017. Myeloid-derived suppressor cells promote B-cell production of IgA in a TNFR2-dependent manner.Cell Mol Immunol, 14(7):597-606.

22. Shao W, Zhang C, Liu E, Zhang L, Ma J, Zhu Z, Gong X,Qin Z*,Qiu X*. 2016. Identification of Liver Epithelial Cell-derived Ig Expression in mu chain-deficient mice.Sci Rep6: 23669

23. Atretkhany KS, Nosenko MA, Gogoleva VS, Zvartsev RV,Qin Z,Nedospasov SA, Drutskaya MS*. 2016. TNF Neutralization Results in the Delay of Transplantable Tumor Growth and Reduced MDSC Accumulation.Front Immunol7: 147

24. Xu X, Meng Q, Erben U, Wang P, Glauben R, Kuhl AA, Wu H, Ma CW, Hu M, Wang Y, Sun W, Jia J, Wu X, Chen W, Siegmund B, Qin Z*. 2016. Myeloid-derived suppressor cells promote B-cell production of IgA in a TNFR2-dependent manner.Cell Mol Immunol.

25. Chen L, Li J, Wang F, Dai C, Wu F, Liu X, Li T, Glauben R, Zhang Y, Nie G, He Y*,Qin Z*.2016. Tie2 expression on macrophages is required for blood vessel reconstruction and tumor relapse after chemotherapy.Cancer Res

26. Ji T, Zhao Y, Ding Y, Wang J, Zhao R, Lang J, Qin H, Liu X, Shi J, Tao N,Qin Z, Nie G*. 2016. Transformable Peptide Nanocarriers for Expeditious Drug Release and Effective Cancer Therapy via Cancer-Associated Fibroblast Activation.Angew Chem Int Ed Engl. 55(3): 1050–1055.

27. Sun L, Sun C, Liang Z, Li H, Chen L, Luo H, Zhang H, Ding P, Sun X,Qin Z*,Zhao Y*. 2015. FSP1(+) fibroblast subpopulation is essential for the maintenance and regeneration of medullary thymic epithelial cells.Sci Rep5: 14871

28. Yang S, Wang Y, Mei K, Zhang S, Sun X, Ren F, Liu S, Yang Z, Wang X,Qin Z, Chang Z*. 2015. Tumor necrosis factor receptor 2 (TNFR2).interleukin-17 receptor D (IL-17RD) heteromerization reveals a novel mechanism for NF-kappaB activation.J Biol Chem290: 861-71

29. Xu M, Liu M, Du X, Li S, Li H, Li X, Li Y, Wang Y,Qin Z, Fu YX*, Wang S*. 2015. Intratumoral Delivery of IL-21 Overcomes Anti-Her2/Neu Resistance through Shifting Tumor-Associated Macrophages from M2 to M1 Phenotype.J Immunol194: 4997-5006

30. Zhang J*, Ni C, Yang Z, Piontek A, Chen H, Wang S, Fan Y,Qin Z, Piontek J. 2015. Specific binding of Clostridium perfringens enterotoxin fragment to Claudin-b and modulation of zebrafish epidermal barrier.Exp Dermatol24: 605-10

31. Ji T, Ding Y, Zhao Y, Wang J, Qin H, Liu X, Lang J, Zhao R, Zhang Y, Shi J, Tao N,Qin Z*,Nie G*. 2015. Peptide assembly integration of fibroblast-targeting and cell-penetration features for enhanced antitumor drug delivery.Adv Mater27: 1865-73

32. Chen L, Li J, Zhang J, Dai C, Liu X, Wang J, Gao Z, Guo H, Wang R, Lu S, Wang F, Zhang H, Chen H, Fan X, Wang S,Qin Z*.2015. S100A4 promotes liver fibrosis via activation of hepatic stellate cells.J Hepatol62: 156-64

33. Xing S, Luo Y, Liu Z, Bu P, Duan H, Liu D, Wang P, Yang J, Song L, Feng J, Yang D,Qin Z, Yan X*. 2014. Targeting endothelial CD146 attenuates colitis and prevents colitis-associated carcinogenesis.Am J Pathol184: 1604-16

34. Ni C, Wang C, Zhang J, Qu L, Liu X, Lu Y, Yang W, Deng J, Lorenz D, Gao P, Meng Q, Yan X, Blasig IE,Qin Z*.2014. Interferon-gamma Safeguards Blood-Brain Barrier during Experimental Autoimmune Encephalomyelitis.Am J Pathol184: 3308-20

35. Hu X, Li B, Li X, Zhao X, Wan L, Lin G, Yu M, Wang J, Jiang X, Feng W,Qin Z, Yin B*, Li Z*. 2014. Transmembrane TNF-alpha promotes suppressive activities of myeloid-derived suppressor cells via TNFR2.J Immunol 192: 1320-31

36. Gao P, Tao N, Ma Q, Fan WX, Ni C, Wang H,Qin ZH*.2014. DH332, a synthetic beta-carboline alkaloid, inhibits B cell lymphoma growth by activation of the caspase family.Asian Pac J Cancer Prev15: 3901-6

37. Deng J, Liu X, Rong L, Ni C, Li X, Yang W, Lu Y, Yan X, Qin C, Zhang L,Qin Z*.2014. IFNgamma-responsiveness of endothelial cells leads to efficient angiostasis in tumours involving down-regulation of Dll4.J Pathol233: 170-82

38. Zhang J, Chen L, Liu X, Kammertoens T, Blankenstein T,Qin Z*.2013. Fibroblast-Specific Protein 1/S100A4-Positive Cells Prevent Carcinoma through Collagen Production and Encapsulation of Carcinogens.Cancer Res73: 2770-81

39. Zhang G, Liu X, Wang C, Qu L, Deng J, Wang H,Qin Z*.2013. Resolution of PMA-induced skin inflammation involves interaction of IFN-gamma and ALOX15.Mediators Inflamm2013: 930124

40. Wang J, Wang X, Gao C, Song X, Niu Z, Gao Z,Qin Z, Chang J*, Wang H*. 2013. The pyrimidine analog FNC inhibits cell proliferation and viral protein synthesis in HTLV1infected cells.Mol Med Rep7: 1656-60

41. Wang J, Niu Z, Shi Y, Gao C, Wang X, Han J, Li J, Gao Z, Zhu X, Song X,Qin Z*,Wang H*. 2013. Bcl-3, induced by Tax and HTLV-1, inhibits NF-kappaB activation and promotes autophagy.Cell Signal25: 2797-804

42. Wang C, Xiao M, Liu X, Ni C, Liu J, Erben U, Qin Z*. 2013. IFN-gamma-mediated downregulation of LXA4 is necessary for the maintenance of nonresolving inflammation and papilloma persistence.Cancer Res73: 1742-51

43. Rothe M, Quarcoo D, Chashchina AA, Bozrova SV,Qin Z, Nedospasov SA, Blankenstein T, Kammertoens T*, Drutskaya MS. 2013. IL-13 but not IL-4 signaling via IL-4Ralpha protects mice from papilloma formation during DMBA/TPA two-step skin carcinogenesis.Cancer Med2: 815-25

44. Deng J, Zhao X, Rong L, Li X, Liu X,Qin Z*.2013. TNFR-1 on tumor cells contributes to the sensitivity of fibrosarcoma to chemotherapy.Protein Cell4: 393-401

45. Zhao X, Rong L, Li X, Liu X, Deng J, Wu H, Xu X, Erben U, Wu P, Syrbe U, Sieper J,Qin Z*.2012. TNF signaling drives myeloid-derived suppressor cell accumulation.J Clin Invest122: 4094-104

46. Wu H, Tao N, Liu X, Li X, Tang J, Ma C, Xu X, Shao H, Hou B, Wang H,Qin Z*. 2012. Polysaccharide from Lentinus edodes inhibits the immunosuppressive function of myeloid-derived suppressor cells.PLoS One7: e51751

47. Li J, Chen L,Qin Z*.2012. Multifaceted tumor stromal fibroblasts.Cancer Microenviron5: 187-93

48. Kammertoens T,Qin Z,Briesemeister D, Bendelac A, Blankenstein T*. 2012. B-cells and IL-4 promote methylcholanthrene-induced carcinogenesis but there is no evidence for a role of T/NKT-cells and their effector molecules (Fas-ligand, TNF-alpha, perforin).Int J Cancer131: 1499-508

49. Zhang J, Chen L, Xiao M, Wang C,Qin Z*.2011. FSP1+ fibroblasts promote skin carcinogenesis by maintaining MCP-1-mediated macrophage infiltration and chronic inflammation.Am J Pathol178: 382-90

50. Yang W, Ding X, Deng J, Lu Y, Matsuda Z, Thiel A, Chen J, Deng H,Qin Z*.2011. Interferon-gamma negatively regulates Th17-mediated immunopathology during mouse hepatitis virus infection.J Mol Med(Berl) 89: 399-409

51. Lv J, Tao N, Wu H, Liu X, Xu X, Xu Y,Qin Z*.2011. Selective expansion and enhanced anti-tumor effect of antigen-specific CD4(+) T cells by retrovirus-mediated IL-15 expression.Protein Cell2: 585-99

52. Liu S, Rong L, Deng J, Zhao X, Liu X, Xu X,Qin Z*.2011. TNFR2 expression on non-bone marrow-derived cells is crucial for lipopolysaccharide-induced septic shock and downregulation of soluble TNFR2 level in serum.Cell Mol Immunol8: 164-71

53. Ding X, Yang W, Shi X, Du P, Su L,Qin Z*,Chen J*, Deng H*. 2011. TNF receptor 1 mediates dendritic cell maturation and CD8 T cell response through two distinct mechanisms.J Immunol187: 1184-91

54. Chen H, Sun H, You F, Sun W, Zhou X, Chen L, Yang J, Wang Y, Tang H, Guan Y, Xia W, Gu J, Ishikawa H, Gutman D, Barber G,Qin Z,Jiang Z*. 2011. Activation of STAT6 by STING is critical for antiviral innate immunity.Cell147: 436-46

55. Wang Z, Jiang J, Li Z, Zhang J, Wang H,Qin Z*.2010. A myeloid cell population induced by Freund adjuvant suppresses T-cell-mediated antitumor immunity.J Immunother33: 167-77

56. Li J, Lu Y, Zhang J, Kang H,Qin Z*,Chen C. 2010. PI4KIIalpha is a novel regulator of tumor growth by its action on angiogenesis and HIF-1alpha regulation.Oncogene29: 2550-9

57. Jiang J, Wang Z, Li Z, Zhang J, Wang C, Xu X,Qin Z*.2010. Early exposure of high-dose interleukin-4 to tumor stroma reverses myeloid cell-mediated T-cell suppression.Gene Ther17: 991-9

58. He XH, Zang Y, Chen X, Pang RP, Xu JT, Zhou X, Wei XH, Li YY, Xin WJ,Qin ZH,Liu XG*. 2010. TNF-alpha contributes to up-regulation of Nav1.3 and Nav1.8 in DRG neurons following motor fiber injury.Pain151: 266-79

59. Xiao M, Wang C, Zhang J, Li Z, Zhao X,Qin Z*.2009. IFNgamma promotes papilloma development by up-regulating Th17-associated inflammation.Cancer Res69: 2010-7

60. Lu Y, Yang W, Qin C, Zhang L, Deng J, Liu S,Qin Z*.2009. Responsiveness of stromal fibroblasts to IFN-gamma blocks tumor growth via angiostasis.J Immunol183: 6413-21

61. Li Z, Chen L,Qin Z*.2009. Paradoxical roles of IL-4 in tumor immunity.Cell Mol Immunol6: 415-22

62. Li Z, Jiang J, Wang Z, Zhang J, Xiao M, Wang C, Lu Y,Qin Z*.2008. Endogenous interleukin-4 promotes tumor development by increasing tumor cell resistance to apoptosis.Cancer Res68: 8687-94

63. Kuprash DV*,Qin Z,Ito D, Grivennikov SI, Abe K, Drutskaya LN, Blankenstein T, Nedospasov SA. 2008. Ablation of TNF or lymphotoxin signaling and the frequency of spontaneous tumors in p53-deficient mice.Cancer Lett268: 70-5

64. Zhao X, Mohaupt M, Jiang J, Liu S, Li B,Qin Z*.2007. Tumor necrosis factor receptor 2-mediated tumor suppression is nitric oxide dependent and involves angiostasis.Cancer Res67: 4443-50

65. Li Z, Pradera F, Kammertoens T, Li B, Liu S,Qin Z*.2007. Cross-talk between T cells and innate immune cells is crucial for IFN-gamma-dependent tumor rejection.J Immunol179: 1568-76

66. Wu TH*, Pabin CN,Qin Z, Blankenstein T, Philip M, Dignam J, Schreiber K, Schreiber H. 2004. Long-term suppression of tumor growth by TNF requires a Stat1- and IFN regulatory factor 1-dependent IFN-gamma pathway but not IL-12 or IL-18.J Immunol172: 3243-51

67.Qin Z, Blankenstein T*. 2004. A cancer immunosurveillance controversy.Nat Immunol5: 3-4; author reply -5

68. Kim HJ, Kammertoens T, Janke M, Schmetzer O,Qin Z, Berek C, Blankenstein T*. 2004. Establishment of early lymphoid organ infrastructure in transplanted tumors mediated by local production of lymphotoxin alpha and in the combined absence of functional B and T cells.J Immunol172: 4037-47

69.Qin Z*,Schwartzkopff J, Pradera F, Kammertoens T, Seliger B, Pircher H, Blankenstein T. 2003. A critical requirement of interferon gamma-mediated angiostasis for tumor rejection by CD8+ T cells.Cancer Res63: 4095-100

70. Guo J, Zhang M, Wang B, Yuan Z, Guo Z, Chen T, Yu Y,Qin Z, Cao X*. 2003. Fractalkine transgene induces T-cell-dependent antitumor immunity through chemoattraction and activation of dendritic cells.Int J Cancer103: 212-20

71. Guo J, Chen T, Wang B, Zhang M, An H, Guo Z, Yu Y,Qin Z, Cao X*. 2003. Chemoattraction, adhesion and activation of natural killer cells are involved in the antitumor immune response induced by fractalkine/CX3CL1.Immunol Lett89: 1-7

72. Blankenstein T,Qin Z*.2003. Chemical carcinogens as foreign bodies and some pitfalls regarding cancer immune surveillance.Adv Cancer Res90: 179-207

73. Blankenstein T,Qin Z*.2003. The role of IFN-gamma in tumor transplantation immunity and inhibition of chemical carcinogenesis.Curr Opin Immunol15: 148-54

74. Yu Y, Liu S, Wang W, Song W, Zhang M, Zhang W,Qin Z, Cao X*. 2002. Involvement of tumour necrosis factor-alpha-related apoptosis-inducing ligand in enhanced cytotoxicity of lipopolysaccharide-stimulated dendritic cells to activated T cells.Immunology106: 308-15

75.Qin Z*,Kim HJ, Hemme J, Blankenstein T. 2002. Inhibition of methylcholanthrene-induced carcinogenesis by an interferon gamma receptor-dependent foreign body reaction.J Exp Med195: 1479-90

76.Qin Z*,Harders C, Cao X, Huber C, Blankenstein T, Seliger B. 2002. Increased tumorigenicity, but unchanged immunogenicity, of transporter for antigen presentation 1-deficient tumors.Cancer Res62: 2856-60

77. Guo J, Wang B, Zhang M, Chen T, Yu Y, Regulier E, Homann HE,Qin Z, Ju DW, Cao X*. 2002. Macrophage-derived chemokine gene transfer results in tumor regression in murine lung carcinoma model through efficient induction of antitumor immunity.Gene Ther9: 793-803

78. An H, Yu Y, Zhang M, Xu H, Qi R, Yan X, Liu S, Wang W, Guo Z, Guo J,Qin Z, Cao X*. 2002. Involvement of ERK, p38 and NF-kappaB signal transduction in regulation of TLR2, TLR4 and TLR9 gene expression induced by lipopolysaccharide in mouse dendritic cells.Immunology106: 38-45

79. An H, Xu H, Yu Y, Zhang M, Qi R, Yan X, Liu S, Wang W, Guo Z,Qin Z, Cao X*. 2002. Up-regulation of TLR9 gene expression by LPS in mouse macrophages via activation of NF-kappaB, ERK and p38 MAPK signal pathways.Immunol Lett81: 165-9

80. Ibe S,Qin Z*,Schuler T, Preiss S, Blankenstein T. 2001. Tumor rejection by disturbing tumor stroma cell interactions.J Exp Med194: 1549-59

81. Cayeux S*,Qin Z, Dorken B, Blankenstein T. 2001. Decreased generation of anti-tumor immunity after intrasplenic immunization.Eur J Immunol31: 1392-9

82. Westermann J*, Kopp J, Korner I, Richter G,Qin Z, Blankenstein T, Dorken B, Pezzutto A. 2000. Bcr/abl+ autologous dendritic cells for vaccination in chronic myeloid leukemia.Bone Marrow Transplant25 Suppl 2: S46-9

83.Qin Z*,Blankenstein T. 2000. CD4+ T cell--mediated tumor rejection involves inhibition of angiogenesis that is dependent on IFN gamma receptor expression by nonhematopoietic cells.Immunity12: 677-86

84. Schuler T*,Qin Z, Ibe S, Noben-Trauth N, Blankenstein T. 1999. T helper cell type 1-associated and cytotoxic T lymphocyte-mediated tumor immunity is impaired in interleukin 4-deficient mice.J Exp Med189: 803-10

85. Westermann J*, Aicher A,Qin Z, Cayeux Z, Daemen K, Blankenstein T, Dorken B, Pezzutto A. 1998. Retroviral interleukin-7 gene transfer into human dendritic cells enhances T cell activation.Gene Ther5: 264-71

86. Uckert W*, Kammertons T, Haack K,Qin Z, Gebert J, Schendel DJ, Blankenstein T. 1998. Double suicide gene (cytosine deaminase and herpes simplex virus thymidine kinase) but not single gene transfer allows reliable elimination of tumor cells in vivo.Hum Gene Ther9: 855-65

87. Tong B, Grimes HL, Yang TY, Bear SE,Qin Z, Du K, El-Deiry WS, Tsichlis PN*. 1998. The Gfi-1B proto-oncoprotein represses p21WAF1 and inhibits myeloid cell differentiation.Mol Cell Biol18: 2462-73

88.Qin Z*,Richter G, Schuler T, Ibe S, Cao X, Blankenstein T. 1998. B cells inhibit induction of T cell-dependent tumor immunity.Nat Med4: 627-30

89. Petersson M*, Charo J, Salazar-Onfray F, Noffz G, Mohaupt M,Qin Z, Klein G, Blankenstein T, Kiessling R. 1998. Constitutive IL-10 production accounts for the high NK sensitivity, low MHC class I expression, and poor transporter associated with antigen processing (TAP)-1/2 function in the prototype NK target YAC-1.J Immunol161: 2099-105

90. Noffz G*,Qin Z, Kopf M, Blankenstein T. 1998. Neutrophils but not eosinophils are involved in growth suppression of IL-4-secreting tumors.J Immunol160: 345-50

91. Salazar-Onfray F*, Charo J, Petersson M, Freland S, Noffz G,Qin Z, Blankenstein T, Ljunggren HG, Kiessling R. 1997. Down-regulation of the expression and function of the transporter associated with antigen processing in murine tumor cell lines expressing IL-10.J Immunol159: 3195-202

92.Qin Z*,Noffz G, Mohaupt M, Blankenstein T. 1997. Interleukin-10 prevents dendritic cell accumulation and vaccination with granulocyte-macrophage colony-stimulating factor gene-modified tumor cells.J Immunol159: 770-6

93.Qin Z*,Blankenstein T. 1996. Influence of local cytokines on tumor metastasis: using cytokine gene-transfected tumor cells as experimental models.Curr Top Microbiol Immunol213 ( Pt 3): 55-64

94. Blankenstein T*,Qin Z*.1996. Cancer vaccines in gene therapy.Gene Ther3: 95-6

95. Blankenstein T*, Cayeux S, Qin Z. 1996. Genetic approaches to cancer immunotherapy.Rev Physiol Biochem Pharmacol129: 1-49

96.Qin Z*,van Tits LJ, Buurman WA, Blankenstein T. 1995. Human lymphotoxin has at least equal antitumor activity in comparison to human tumor necrosis factor but is less toxic in mice.Blood85: 2779-85

97.Qin Z*,Blankenstein T. 1995. Tumor growth inhibition mediated by lymphotoxin: evidence of B lymphocyte involvement in the antitumor response.Cancer Res55: 4747-51

98. Hock H, Dorsch M, Richter G, Kunzendorf U, Kruger-Krasagakes S, Blankenstein T,Qin Z, Diamantstein T*. 1994. Tumor-cell-targeted cytokine gene transfer in experimental models for cancer therapy.Nat Immun13: 85-92

99.Qin Z*,Kruger-Krasagakes S, Kunzendorf U, Hock H, Diamantstein T, Blankenstein T. 1993. Expression of tumor necrosis factor by different tumor cell lines results either in tumor suppression or augmented metastasis.J Exp Med178: 355-60

100. Hock H*, Dorsch M, Kunzendorf U, Uberla K,Qin Z,Diamantstein T, Blankenstein T. 1993. Vaccinations with tumor cells genetically engineered to produce different cytokines: effectivity not superior to a classical adjuvant.Cancer Res53: 714-6

101. Hock H*, Dorsch M, Kunzendorf U,Qin Z, Diamantstein T, Blankenstein T. 1993. Mechanisms of rejection induced by tumor cell-targeted gene transfer of interleukin 2, interleukin 4, interleukin 7, tumor necrosis factor, or interferon gamma.Proc Natl Acad Sci U S A90: 2774-8

102. Foss HD, Herbst H*, Oelmann E, Samol J, Grebe M, Blankenstein T, Matthes J,Qin ZH, Falini B, Pileri S, et al. 1993. Lymphotoxin, tumour necrosis factor and interleukin-6 gene transcripts are present in Hodgkin and Reed-Sternberg cells of most Hodgkin's disease cases.Br J Haematol84: 627-35

103. Uberla K, Li WQ,Qin ZH, Richter G, Raabe T, Diamantstein T, Blankenstein T*. 1991. The rat interleukin-5 gene: characterization and expression by retroviral gene transfer and polymerase chain reaction.Cytokine3: 72-81

104.Qin ZH, Schuller I, Richter G, Diamantstein T, Blankenstein T*. 1991. The interleukin-6 gene locus seems to be a preferred target site for retrotransposon integration.Immunogenetics33: 260-6

105. Blankenstein T*,Qin ZH, Uberla K, Muller W, Rosen H, Volk HD, Diamantstein T. 1991. Tumor suppression after tumor cell-targeted tumor necrosis factor alpha gene transfer.J Exp Med173: 1047-52

106. Zheng ZQ*,Qin ZH, Ma AY, Qiao CX, Wang H. 1990. Detection of early pregnancy factor-like activity in human amniotic fluid.Am J Reprod Immunol22: 9-11

107. Blankenstein T*,Qin ZH, Li WQ, Diamantstein T. 1990. DNA rearrangement and constitutive expression of the interleukin 6 gene in a mouse plasmacytoma.J Exp Med171: 965-70

108. Blankenstein T,Qin Z, Uberla K, Volk HD*, Diamantstein T. 1990. Tumor cell targeted cytokine (TNF-alpha) gene therapy for cancer.Immunol Today11: 431

109. Blankenstein T*, Li WQ, Uberla K,Qin ZH, Tominaga A, Takatsu K, Yamaguchi N, Diamantstein T. 1990. Retroviral interleukin 5 gene transfer into interleukin 5-dependent growing cell lines results in autocrine growth and tumorigenicity.Eur J Immunol20: 2699-705

110. Richter G,Qin ZH, Diamantstein T*, Blankenstein T. 1989. Analysis of restriction fragment length polymorphism in lymphokine genes of normal and autoimmune mice.J Exp Med170: 1439-43

111. Qin Z, Richter G, Diamantstein T*, Blankenstein T. 1989. Structure and evolution of mouse interleukin 6 gene.Mol Immunol26: 1021-6

112. Blankenstein T*, Volk HD, Techert-Jendrusch C,Qin ZH, Richter G, Diamantstein T. 1989. Lack of correlation between BglII RFLP in the human interleukin 6 gene and rheumatoid arthritis.Nucleic Acids Res17: 8902

113.Qin ZH, Zheng ZQ*. 1987. Detection of early pregnancy factor in human sera.Am J Reprod Immunol Microbiol13: 15-8

专利申请:

1. 2012.5 中国 重组逆转录病毒载体。秦志海;吕继洲;徐迎新

2. 2014.5 中国 S100A4秦志海;陈琳;李洁

(资料来源:秦志海研究员,2020-11-16)

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