秦志海

  • 秦志海
  • 简历 & 研究组工作摘要

      1987年-1992年:柏林自由大学免疫所 获医学博士学位

      1992年-1994年:美国Fox Chase癌症研究中心 博士后

      1994年-2000年:德国MDC分子医学中心 课题组长

      2000年-2005年:柏林自由大学 终生研究员,于2005年辞职

      2005年-今: 中国科学院生物物理研究所

      近年来,在肿瘤免疫学领域,尤其是在“炎性因子与肿瘤”方面的研究成果斐然,已发表学术论文近七十篇,其代表性成果发表在Immunity、Nature Immunology、Nature Medicine、Journal of Experimental Medicine、Cancer Research等国际著名学术期刊上,他人引用次数高达2600多次。

      肿瘤是由恶变的肿瘤细胞和肿瘤间质细胞(主要包括成纤维细胞、血管内皮细胞、浸润的免疫抑制细胞等)组成。间质细胞在肿瘤发生发展中发挥重要的作用。肿瘤细胞与间质细胞的关系常被比作“种子”与“土壤”。近年来,对于肿瘤间质细胞的研究越来越受到重视,是肿瘤研究的前沿热点。

      课题组一直关注于肿瘤微环境中多种间质细胞如成纤维细胞、血管内皮细胞和巨噬细胞在肿瘤发生、发展中的作用及分子机制研究,相继发现:

      (1)干扰素γ的抗血管新生作用是其诱导肿瘤免疫排斥的主要机制,该成果获得2007年北京市科技进步奖。

      (2)在化学物致癌过程中,成纤维细胞既能够通过招募巨噬细胞,促进慢性炎症和肿瘤发生;也能够通过”异物反应”,包裹致癌物,抑制肿瘤发生。成纤维细胞在肿瘤不同部位、肿瘤发生不同时间的作用和具体机制还有待进一步研究。

      (3)内源性的肿瘤坏死因子(Tumor necrosis factor, TNF)通过TNFR2介导的存活信号,维持髓样抑制性细胞在肿瘤和外周的聚集,促进肿瘤生长。

      目前研究方向主要集中在以下几个方面:

      (1)肿瘤微环境的形成机制:炎症因子诱导免疫负调控细胞的形成机制;炎症因子在肿瘤生长及转移中的效应机制研究;炎症因子在炎症相关肿瘤发生过程中的机制研究。

      (2)肿瘤细胞与各间质细胞间的相互作用:利用移植瘤和化学致癌模型,研究肿瘤发生、生长、转移和化疗过程中,成纤维细胞、巨噬细胞、血管内皮细胞的作用及机制研究。

      (3)采用生物技术改变肿瘤微环境:靶向免疫负调控细胞的肿瘤治疗新策略研究。

      项目资助:

      1. 国家重点基础研究发展计划(973 计划),恶性肿瘤免疫负调控分子网络的形成与干预,首席科学家,2012.1-2016.12

      2. 国家自然科学基金重大专项,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

      3. 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

      4. 国家自然科学基金面上项目,利用逆转录病毒研究肿瘤间质细胞的基因不稳定性,2011.1-2013.12

      代表性论文: (*corresponding author)

      1. 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 Pathol 184: 1604-16

      2. 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-γ safeguards blood-brain barrier during 1 experimental autoimmune encephalomyelitis. Am J Pathol

      3. 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

      4. 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 Prev 15: 3901-6

      5. 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 Pathol 233: 170-82

      6. 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. 2014. S100A4 promotes liver fibrosis via activation of hepatic stellate cells. J Hepatol

      7. Zhang, J., L. Chen, X. Liu, T. Kammertoens, T. Blankenstein, and Z. Qin*, Fibroblast-Specific Protein 1/S100A4-Positive Cells Prevent Carcinoma through Collagen Production and Encapsulation of Carcinogens. Cancer Research, 2013. 73(9): p. 2770-81.

      8. Wang, C., M. Xiao, X. Liu, C. Ni, J. Liu, U. Erben, and Z. Qin*, IFN-gamma-Mediated Downregulation of LXA4 Is Necessary for the Maintenance of Nonresolving Inflammation and Papilloma Persistence. Cancer Research, 2013. 73(6): p. 1742-51.

      9.  Wu, H., N. Tao, X. Liu, X. Li, J. Tang, C. Ma, X. Xu, H. Shao, B. Hou, H. Wang, and Z. Qin*, Polysaccharide from Lentinus edodes inhibits the immunosuppressive function of myeloid-derived suppressor cells. PLoS One, 2012. 7(12): p. e51751.

      10.  Zhao X, Rong L, Zhao X, Li X, Liu X, Deng J, Wu H, Xu X, Erben U, WU P, Syrbe U, Sieper J, Qin Z*. TNFR-2 dependent caspase-8 repression is necessary for peripheral MDSC accumulation. J Clin Invest, 2012. 122(11): p. 4094-104

      11.  Li, J., L. Chen, and Z. Qin*, Multifaceted tumor stromal fibroblasts. Cancer Microenviron, 2012. 5(3): p. 187-93

      12.  Zhang, J., L. Chen, M. Xiao, C. Wang, and Z. Qin*, FSP1+ fibroblasts promote skin carcinogenesis by maintaining MCP-1-mediated macrophage infiltration and chronic inflammation. Am J Pathol, 2011. 178(1): p. 382-90.

      13.  Yang, W., X. Ding, J. Deng, Y. Lu, Z. Matsuda, A. Thiel, J. Chen, H. Deng, and Z. Qin*, Interferon-gamma negatively regulates Th17-mediated immunopathology during mouse hepatitis virus infection. J Mol Med, 2011. 89(4): p. 399-409.

      14.  Ding, X., W. Yang, X. Shi, P. Du, L. Su, Z. Qin*, J. Chen*, and H. Deng*, TNF receptor 1 mediates dendritic cell maturation and CD8 T cell response through two distinct mechanisms. J Immunol, 2011. 187(3): p. 1184-91.

      15.  Chen, H., H. Sun, F. You, W. Sun, X. Zhou, L. Chen, J. Yang, Y. Wang, H. Tang, Y. Guan, W. Xia, J. Gu, H. Ishikawa, D. Gutman, G. Barber, Z. Qin, and Z. Jiang, Activation of STAT6 by STING is critical for antiviral innate immunity. Cell, 2011. 147(2): p. 436-46.

      16.  Wang, Z., J. Jiang, Z. Li, J. Zhang, H. Wang, and Z. Qin*, A myeloid cell population induced by Freund adjuvant suppresses T-cell-mediated antitumor immunity. J Immunother, 2010. 33(2): p. 167-77.

      17.  Li, J., Y. Lu, J. Zhang, H. Kang, Z. Qin*, and C. Chen*, PI4KIIalpha is a novel regulator of tumor growth by its action on angiogenesis and HIF-1alpha regulation. Oncogene, 2010. 29(17): p. 2550-9.

      18.  Jiang, J., Z. Wang, Z. Li, J. Zhang, C. Wang, X. Xu, and Z. Qin*, Early exposure of high-dose interleukin-4 to tumor stroma reverses myeloid cell-mediated T-cell suppression. Gene Ther, 2010. 17(8): p. 991-9.

      19.  Xiao, M., C. Wang, J. Zhang, Z. Li, X. Zhao, and Z. Qin*, IFNgamma promotes papilloma development by up-regulating Th17-associated inflammation. Cancer Research, 2009. 69(5): p. 2010-7.

      20.  Lu, Y., W. Yang, C. Qin, L. Zhang, J. Deng, S. Liu, and Z. Qin*, Responsiveness of stroma fibroblasts to IFN-gamma blocks tumor growth via angiostasis. J Immunol, 2009. 183(10): p. 6413-21.

      21.  Li, Z., L. Chen, and Z. Qin*, Paradoxical roles of IL-4 in tumor immunity. Cell Mol Immunol, 2009. 6(6): p. 415-22.

      22.  Li, Z., J. Jiang, Z. Wang, J. Zhang, M. Xiao, C. Wang, Y. Lu, and Z. Qin*, Endogenous interleukin-4 promotes tumor development by increasing tumor cell resistance to apoptosis. Cancer Research, 2008. 68(21): p. 8687-94.

      23.  Zhao, X., M. Mohaupt, J. Jiang, S. Liu, B. Li, and Z. Qin*, Tumor necrosis factor receptor 2-mediated tumor suppression is nitric oxide dependent and involves angiostasis. Cancer Research, 2007. 67(9): p. 4443-50.

      24.  Li, Z., F. Pradera, T. Kammertoens, B. Li, S. Liu, and Z. Qin*, Cross-talk between T cells and innate immune cells is crucial for IFN-gamma-dependent tumor rejection. J Immunol, 2007. 179(3): p. 1568-76.

      25.  Qin, Z. and T. Blankenstein, A cancer immunosurveillance controversy. Nat Immunol, 2004. 5(1): p. 3-4; author reply 4-5.

      26.  Qin, Z.*, J. Schwartzkopff, F. Pradera, T. Kammertoens, B. Seliger, H. Pircher, and T. Blankenstein, A critical requirement of interferon gamma-mediated angiostasis for tumor rejection by CD8+ T cells. Cancer Research, 2003. 63(14): p. 4095-100.

      27.  Blankenstein, T. and Z. Qin*, Chemical carcinogens as foreign bodies and some pitfalls regarding cancer immune surveillance. Adv Cancer Res, 2003. 90: p. 179-207.

      28.  Blankenstein, T. and Z. Qin*, The role of IFN-gamma in tumor transplantation immunity and inhibition of chemical carcinogenesis. Curr Opin Immunol, 2003. 15(2): p. 148-54.

      29.  Qin, Z. *, H.J. Kim, J. Hemme, and T. Blankenstein, Inhibition of methylcholanthrene-induced carcinogenesis by an interferon gamma receptor-dependent foreign body reaction. J Exp Med, 2002. 195(11): p. 1479-90.

      30.  Qin, Z. *, C. Harders, X. Cao, C. Huber, T. Blankenstein, and B. Seliger, Increased tumorigenicity, but unchanged immunogenicity, of transporter for antigen presentation 1-deficient tumors. Cancer Research, 2002. 62(10): p. 2856-60.

      31.  Ibe, S., Z. Qin*, T. Schuler, S. Preiss, and T. Blankenstein, Tumor rejection by disturbing tumor stroma cell interactions. J Exp Med, 2001. 194(11): p. 1549-59 (also co-first author).

      32.  Qin, Z.* and T. Blankenstein, CD4+ T cell--mediated tumor rejection involves inhibition of angiogenesis that is dependent on IFN gamma receptor expression by nonhematopoietic cells. Immunity, 2000. 12(6): p. 677-86.

      33.  Qin, Z.*, G. Richter, T. Schuler, S. Ibe, X. Cao, and T. Blankenstein, B cells inhibit induction of T cell-dependent tumor immunity. Nat Med, 1998. 4(5): p. 627-30.