EZH2作为抗肿瘤免疫治疗靶点研究进展

doi:10.13560/j.cnki.biotech.bull.1985.2015.01.004

生物技术通报 ›› 2015, Vol. 31 ›› Issue (1): 29-32.doi: 10.13560/j.cnki.biotech.bull.1985.2015.01.004

EZH2作为抗肿瘤免疫治疗靶点研究进展

李倩王艳林

（三峡大学医学院三峡大学分子生物学研究所，宜昌 443002）

收稿日期:2014-05-07 出版日期:2015-01-09 发布日期:2015-01-10
作者简介:李倩，女，硕士研究生，研究方向：肿瘤免疫；E-mail：m15672484851@163.com
基金资助:
国家自然科学基金资助项目（81372265），湖北省高等学校优秀中青年创新团队计划项目（T201203）

Research Progress in EZH2 as a Target for Anti-tumor Immunotherapy

Li Qian, Wang Yanlin

（Medical College，Institute of Molecular Biology，Three Gorges University，Yichang 443002）

Received:2014-05-07 Published:2015-01-09 Online:2015-01-10

摘要/Abstract

摘要： 多梳蛋白复合体（PcG）的核心亚基zeste基因增强子同源物2（Enhancer of zeste homolog2，EZH2）是一种组蛋白甲基转移酶，参与维持细胞密度、干细胞多能性、细胞周期调节等重要的生理作用。研究发现，EZH2在多种肿瘤组织中高表达，是促进肿瘤发生和发展的致癌因子。由于EZH2在正常组织中低表达或者不表达，使其新近被鉴定为一种肿瘤相关抗原。已经在EZH2蛋白分子中鉴定出多条特异性抗原肽，这些抗原肽能激发机体免疫细胞对EZH2表达异常增高肿瘤细胞的杀伤活性。上述研究提示，EZH2可能是一种新的抗肿瘤治疗分子靶点，并在肿瘤免疫治疗中具有潜在的应用价值。就该领域的最新研究进展作一简要综述。

关键词: EZH2, 分子靶点, 抗肿瘤免疫, 肿瘤相关抗原

Abstract: EZH2（enhancer of Zeste homolog2）, the core subunit of polycomb group protein complex（PcG）, is a histone methyltransferase which involves in cell density maintenance, stem cell pluripotent, cell cycle regulation and other important physiological roles. The study has found that EZH2 is over-expressed in many tumor tissues and can be used as a carcinogen to promote tumorigenesis. Since EZH2 has been proved to be non- or low-expressed in normal tissues, it has recently been identified as a tumor-associated antigen. Multiple antigen peptides derived from the EZH2 protein have been identified and their ability in stimulating the killing activity of immune cells against the tumor cells with over-expressed EZH2 has been proved. These studies indicate that EZH2 could be a new molecular target for anti-tumor therapy and has potential value in tumor immunotherapy. This paper gives a brief review on the research progress in these study fields.

Key words: EZH2, molecular target, anti-tumor immunology, tumor-associated antigen

李倩,王艳林,. EZH2作为抗肿瘤免疫治疗靶点研究进展[J]. 生物技术通报, 2015, 31(1): 29-32.

Li Qian, Wang Yanlin. Research Progress in EZH2 as a Target for Anti-tumor Immunotherapy[J]. Biotechnology Bulletin, 2015, 31(1): 29-32.

参考文献

[1] Margueron R, Reinberq D. The Polycomb complex PRC2 and its mark in life[J]. Nature, 2011, 469（7330）：343-349.
[2] Benetatos L, Vartholomatos G, Hatzimichael E. Polycomb group proteins and MYC：thecancerconnection[J]. Cell Mol Life Sci, 2014, 71（2）：257-269.
[3] Chang CJ, Hung MC. The role ofEZH2in tumour progression[J]. Br J Cancer, 2012, 106（2）：243-247.
[4] Crea F, Paolicchi E, Marquez VE, et al. Polycomb genes andcancer：time for clinical application?[J]. Crit Rev Oncol Hematol, 2012, 83（2）：184-193.
[5] Chen H, Rossier C, Antonarakis SE. Cloning of a human homolog of the Drosophila enhancer of zeste gene（EZH2）that maps to enchromosome 21q22.2[J]. Genomies, 1996, 38（1）：30-37.
[6] Cardoso C, Timsit S, Villard L, et al. Specific interaction between the XNP/ATP-X gene product and the SET domain of the human EZH2 protein[J]. Hum Mol Genet, 1998, 7（4）：679-684.
[7] Kim W, Bird GH, Neff T, et al. Target disruption of the EZH2-EED complex inhibits EZH2-dependent cancer[J]. Nature Chemical Biology, 2013, 9（10）：643-650.
[8] Abdel-Wahab O, Levine RL. EZH2 mutations：mutating the epigenetic machinery in myeloid malignancies[J]. Cancer cell, 2010, 18（2）：105-107.
[9] Yaswen P. HDAC inhibitors conquer polycomb proteins[J]. Cell Cycle, 2010, 9（14）：2705.
[10] Viré E, Brenner C, Deplus R, et al. The Polycomb group protein EZH2 directly controls DNA methylation[J]. Nature, 2006, 439（7078）：871-874.
[11] Wan L, Li X, Shen H, et al. Quantitative analysis of EZH2 expression and its correlations with lung cancer patients’ clinical pathological characteristics[J]. Clin Transl Oncol, 2013, 15（2）：132-138.
[12] Coe BP, Thu KL, Aviel-Ronen S, et al. Genomic deregulation of the E2F/Rb pathway leads to activation of the oncogene EZH2 in small lung cancer[J]. PLoS One, 2013, 8（8）：e71670.
[13] Oike T, Oqiwara H, Amornwichet N, et al. Chromatin-regulating proteins as targets for cancer therapy[J]. Journal of Radiation Research, 2014, 55（4）：613-628.
[14] Hwang-Verslues WW, Chang PH, Jeng YM, et al. Loss of corepressor PER2 under hypoxia up-regulates OCT1-mediated EMT gene expression and enhances tumor malignancy[J]. Proc Natl Acad Sci USA， 2013, 110（30）：12331-12336.
[15] Xu K, Wu ZJ, Groner AC, et al. EZH2 oncogenic activity in castra-tion-resistant prostate cancer cells is Polycomb-independent[J]. Science, 2012, 338（6113）：1465-1469.
[16] Hajósi-Kalcakosz S, Dezs? K, Bugyik E, et al. Enhancer of zeste homologue 2（EZH2）is a reliable immunohistochemical marker to differentiate malignant and benign hepatic tumors[J]. Diagn Pathol, 2012, 7：86.
[17] Ma R, Wei Y, Huang X, et al. Inhibition of GSK 3β activity is associated with excessive EZH2 expression and enhanced tumour invasion in nasopharyngeal carcinoma[J]. PLoS One, 2013, 8（7）：e68614.
[18] Ogata R, Matsueda S, Yao A, et al. Identification of polycomb group protein enhancer of zeste homolog2（EZH2）-derived peptides immunogenic in HLA-A24⁺ prostate cancer patients[J]. Prostate, 2004, 60（4）：273-281.
[19] Steele JC, Torr EE, Noakes KL, et al. The polycomb group proteins, BMI-1 and EZH2, are tumour-associated antigens[J]. Br J Cancer, 2006, 95（9）：1202-1211.
[20] Komohara Y, Harada M, Arima Y, et al. Anti-cancer vaccine candidates in specific immunotherapy for bladder carcinoma[J]. Int J Oncol, 2006, 29（6）：1555-1560.
[21] Komohara Y, Harada M, Arima Y, et al. Identification of target antigens in specific immunotherapy for renal cell carcinoma[J]. J Urol, 2007, 177（3）：1157-1162.
[22] Itoh Y, Komohara Y, Komatsu N, et al. New peptides of the polycomb group protein enhancer of zeste homolog 2 with the potential to induce cancer-reactive cytotoxic T lymphocytes in human leukocyte antigen-A2+prostate cancer patients[J]. Oncol Rep, 2007, 18（5）：1231-1237.
[23] Felix NJ, Allen PM. Specificity of T-cell alloreactivity[J]. Nat Rev Immunol, 2007, 7（12）：942-953.
[24] Thiel U, Pirson S, Müller-Spahn C, et al. Specific recognition and inhibition of Ewing tumor growth by antigen-specific allo-restricted cytotoxic T cell[J]. BR J Cancer, 2011, 104（6）：948-956.
[25] Hayashi S, Kumai T, Matsuda Y, et al. Six-transmembrane epithelial antigen of the prostate and enhancer of zeste homolog 2 as immunotherapeutic targets for lung cancer[J]. J Transl Med, 2011, 9：191.

EZH2作为抗肿瘤免疫治疗靶点研究进展

Research Progress in EZH2 as a Target for Anti-tumor Immunotherapy

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 6

编辑推荐

Metrics

本文评价

[1]	崔馨元;薛良义;. 大黄鱼肝细胞肿瘤相关抗原-127基因克隆及分子特征分析[J]. , 2011, 0(11): 125-129.
[2]	李思经. Somatix公司开发口服基因治疗法[J]. , 1996, 0(03): 22-23.
[3]	王颖. 转基因山羊在其乳汁中表达单克隆抗体[J]. , 1995, 0(05): 21-22.
[4]	朱遐. 新的肿瘤相关抗原[J]. , 1994, 0(06): 23-23.
[5]	邓永鸿;. 重组痘苗病毒对癌症可能有免疫和治疗作用[J]. , 1988, 0(04): 19-19.
[6]	. 其它药剂[J]. , 1987, 0(10): 100-103.