高级搜索

黑色素瘤相关抗原-A:食管癌免疫治疗新靶点

刘维华, 桑梅香, 单保恩

刘维华, 桑梅香, 单保恩. 黑色素瘤相关抗原-A:食管癌免疫治疗新靶点[J]. 肿瘤防治研究, 2015, 42(06): 622-626. DOI: 10.3971/j.issn.1000-8578.2015.06.020
引用本文: 刘维华, 桑梅香, 单保恩. 黑色素瘤相关抗原-A:食管癌免疫治疗新靶点[J]. 肿瘤防治研究, 2015, 42(06): 622-626. DOI: 10.3971/j.issn.1000-8578.2015.06.020
LIU Weihua, SANG Meixiang, SHAN Baoen. MAGE-A: New Target of Immunotherapy for Esophageal Cancer[J]. Cancer Research on Prevention and Treatment, 2015, 42(06): 622-626. DOI: 10.3971/j.issn.1000-8578.2015.06.020
Citation: LIU Weihua, SANG Meixiang, SHAN Baoen. MAGE-A: New Target of Immunotherapy for Esophageal Cancer[J]. Cancer Research on Prevention and Treatment, 2015, 42(06): 622-626. DOI: 10.3971/j.issn.1000-8578.2015.06.020

黑色素瘤相关抗原-A:食管癌免疫治疗新靶点

基金项目: 河北省自然科学基金(H2012206077)
详细信息
    作者简介:

    刘维华(1977-),女,博士在读,副主任技师,主要从事肿瘤免疫治疗及研究

    通讯作者:

    单保恩,E-mail: baoenshan1962@hotmail.com

  • 中图分类号: R735.1

MAGE-A: New Target of Immunotherapy for Esophageal Cancer

  • 摘要: 黑色素瘤相关抗原(melanoma-associated antigen, MAGE)-A亚家族是MAGE基因家族成员,属于癌睾丸抗原,包括MAGE-A1~MAGE-A12,定位于X染色体。MAGE-A在正常组织中几乎不表达,而在多种肿瘤组织中表达,其在食管癌细胞系和食管癌组织均有较高表达。MAGE-A基因编码的抗原肽可由食管癌细胞MHCⅠ分子提呈至细胞毒性T细胞,能够发挥特异性抗肿瘤活性。因此,以MAGE-A抗原为新靶点,对食管癌患者进行免疫治疗有良好的前景。

     

    Abstract: Melanoma-associated antigens-A(MAGE-A) are the subfamily of MAGE genes, locate in the human X chromosome and belong to cancer testis antigens(CTA), which are composed of 12 members, MAGE-A1-MAGE-A12. MAGE-A are rarely expressed in normal tissues, but frequently expressed in a variety of tumor tissues, especially highly expressed in esophageal cancer tissues and esophageal carcinoma cell lines. In addition, the peptides encoded by MAGE-A can be presented to cytotoxic T cells(CTL) by MHC Ⅰ molecules in esophageal cancer cells, which plays an important role in anti-tumor activity in a specific manner. Therefore, MAGE-A antigens are of great potential as a new target of immunotherapy in the treatment for esophageal cancer in the future.

     

  • [1] Thomas L. On immunosurveillance in human cancer[J]. Yale J Biol Med, 1982, 55(3-4): 329-33.
    [2] Burnet FM. The concept of immunological surveillance[J]. Prog Exp Tumor Res, 1970, 13: 1-27.
    [3] Katsura Y, Satta Y. Evolutionary history of the cancer immunity antigen MAGE gene family[J]. PLoS One, 2011, 6(6): e20365.
    [4] Mengus C, Schultz-Thater E, Coulot J, et al. MAGE-A10 cancer/ testis antigen is highly expressed in high-grade non-muscleinvasive bladder carcinomas [J]. Int J Cancer, 2013, 132(10): 24 59-63.
    [5] Shantha Kumara HM, Grieco MJ, Caballero OL, et al. MAGE-A3 is highly expressed in a subset of colorectal cancer patients[J]. Cancer Immun, 2012, 12:16.
    [6] Yang XG, Sang MX, Fan XJ, et al. Expressions of MAGE-A4 and P73 protein in breast cancer tissues and their clinical significance[J]. Zhongguo Zhong Liu Sheng Wu Zhi Liao Za Zhi, 20 13, 20(5): 597-602. [杨小岗, 桑梅香, 范晓杰, 等. 乳腺癌组织 中MAGE-A4和P73 蛋白的表达及其临床意义[J]. 中国肿瘤生 物治疗杂志, 2013, 20(5): 597-602.]
    [7] Sang MX, Shan BE, Geng CZ, et al. Expression and function of tumor antigen MAGE-A4 in breast cancer tissues and cell lines[J]. Zhong Liu Fang Zhi Yan Jiu, 2010, 37(4): 407-10. [桑梅香, 单保 恩, 耿翠芝, 等. 肿瘤抗原MAGE-A4在乳腺癌组织和细胞系中 的表达及其作用[J]. 肿瘤防治研究, 2010, 37(4): 407-10.]
    [8] Hou SY, Sang MX, Geng CZ, et al. Expressions of MAGE-A9 and MAGE-A11 in breast cancer and their expression mechanism[J]. Arch Med Res, 2014, 45(1): 44-51.
    [9] Curigliano G, Viale G, Ghioni M, et al. Cancer-testis antigen expression in triple-negative breast cancer[J]. Ann Oncol, 2011, 22 (1): 98-103.
    [10] Karimi S, Mohammadi F, Porabdollah M, et al. Characterization of melanoma-associated antigen-a genes family differential expression in non-small-cell lung cancers[J]. Clin Lung Cancer, 20 12, 13(3): 214-9.
    [11] Cuffel C, Rivals JP, Zaugg Y, et al. Pattern and clinical significance of cancer-testis gene expression in head and neck squamous cell carcinoma[J]. Int J Cancer, 2011, 128(11): 2625-34.
    [12] Pastorcic-Grgic M, Sarcevic B, Dosen D, et al. Prognostic value of MAGE-A and NY-ESO-1 expression in pharyngeal cancer[J]. Head Neck, 2010, 32(9): 1178-84.
    [13] Wilson EM. Androgen receptor molecular biology and potential targets in prostate cancer[J]. Ther Adv Urol, 2010, 2(3): 105-17.
    [14] Xylinas E, Cha EK, Khani F, et al. Association of oncofetal protein expression with clinical outcomes in patients with urothelial carcinoma of the bladder[J]. J Urol, 2014, 191(3): 83 0-41.
    [15] Ayyoub M, Memeo L, Alvarez-Fernández E, et al. Assessment of MAGE-A expression in resected non-small cell lung cancer in relation to clinicopathological features and mutational status of EGFR and KRAS[J]. Cancer Immunol Res, 2014, 2(10): 943-8.
    [16] Zhang S, Zhou X, Yu H, et al. Expression of tumor-specific antigen MAGE, GAGE and BAGE in ovarian cancer tissues and cell lines[J]. BMC Cancer, 2010, 10: 163.
    [17] Peche LY, Scolz M, Ladelfa MF, et al. MageA2 restrains cellular senescence by targeting the function of PMLIV/p53 axis at the PML-NBs[J]. Cell Death Differ, 2012, 19(6): 926-36.
    [18] Nardiello T, Jungbluth AA, Mei A, et al. MAGE-A inhibits apoptosis in proliferating myeloma cells through repression of Bax and maintenance of survivin[J]. Clin Cancer Res, 2011, 17 (13): 4309-19.
    [19] De Smet C, Courtois SJ, Faraoni I, et al. Involvement of two Ets binding sites in the transcriptional activation of the MAGE1 gene[J]. Immunogenetics, 1995, 42(4): 282-90.
    [20] Glazer CA, Smith IM, Ochs MF, et al. Integrative discovery of epigenetically derepressed cancer testis antigens in NSCLC[J]. PLoS One, 2009, 4(12): e8189.
    [21] Krishnadas DK, Bao L, Bai F, et al. Decitabine facilitates immune recognition of sarcoma cells by upregulating CT antigens, MHC molecules, and ICAM-1[J]. Tumour Biol, 2014, 35(6): 5753-62.
    [22] Gunda V, Cogdill AP, Bernasconi MJ, et al. Potential role of 5-aza-2'-deoxycytidine induced MAGE-A4 expression in immunotherapy for anaplastic thyroid cancer[J]. Surgery, 2013, 15 4(6): 1456-62.
    [23] Akers SN, Odunsi K, Karpf AR. Regulation of cancer germline antigen gene expression: implications for cancer immunotherapy[J]. Future Oncol, 2010, 6(5): 717-32.
    [24] Caballero OL, Zhao Q, Rimoldi D, et al. Frequent MAGE mutations in human melanoma[J]. PLoS One, 2010, 5(9): pii: e12773.
    [25] Jia ZC, Ni B, Huang ZM, et al. Identification of two novel HLAA* 02 01-restricted CTL epitopes derived from MAGE-A4[J]. Clin Dev Immunol, 2010, 2010: 567594.
    [26] Chinnasamy N, Wargo JA, Yu Z, et al. A TCR targeting the HLAA* 02 01-restricted epitope of MAGE-A3 recognizes multiple epitopes of the MAGE-A antigen superfamily in several types of cancer[J]. J Immunol, 2011, 186(2): 685-96.
    [27] Zhang YW. Epidemiology of esophageal cancer[J]. World J Gastroenterol, 2013, 19(34): 5598-606.
    [28] Jemal A, Bray F, Center MM, et al. Global cancer statistics[J]. CA Cancer J Clin, 2011, 61(2): 69-90.
    [29] Zhang SW, Zhang M, Li GL, et al. An Analysis of Incidence and Mortality of Esophageal Cancer in China, 2003-2007[J]. Zhongguo Zhong Liu, 2012, 21(4): 241-7. [张思维, 张敏, 李光 琳, 等. 2003~2007年中国食管癌发病与死亡分析[J]. 中国肿瘤, 20 12, 21(4): 241-7.]
    [30] Enzinger PC, Mayer RJ. Esophageal cancer[J]. N Engl J Med, 20 03, 349: 2241-52.
    [31] Inoue H, Mori M, Li J, et al. Human esophageal carcinomas frequently express the tumor-rejection antigens of MAGE genes[J]. Int J Cancer, 1995, 63(4): 523-6.
    [32] Nagashima H, Sadanaga N, Mashino K, et al. Expression of MAGE-B genes in esophageal squamous cell carcinoma[J]. Jpn J Cancer Res, 2001, 92(2): 167-73.
    [33] Forghanifard MM, Gholamin M, Farshchian M, et al. Cancer-testis gene expression profiling in esophageal squamous cell carcinoma: identification of specific tumor marker and potential targets for immunotherapy[J]. Cancer Biol Ther, 2011, 12(3): 191-7.
    [34] Liang Z, Sun ZY, Yuan YH, et al. The expression of 11 cancer / testis (CT) antigen genes in esophageal carcinoma[J]. Zhonghua Zhong Liu Za Zhi, 2005, 27(9): 534-7. [梁震, 孙贞媛, 袁艳华, 等. 11 种癌-睾丸抗原基因在食管癌中表达的检测[J]. 中华肿瘤杂 志, 2005, 27(9): 534-7.]
    [35] Li J, Pan LN, Zhang ZY, et al. Expression of melanoma antigen A1 and its relationship with tumor cell proliferation in esophageal carcinoma[J]. Shi Jie Hua Ren Xiao Hua Za Zhi, 2007, 15(7): 70 6-11.[李佳, 潘林娜, 张志燕, 等. MAGE-A1在食管癌中的表 达及其与肿瘤细胞增殖的关系[J]. 世界华人消化杂志, 2007, 15 (7): 706-11.]
    [36] Haier J, Owzcareck M, Guller U, et al. Expression of MAGE-A cancer/testis antigens in esophageal squamous cell carcinomas[J]. Anticancer Res, 2006, 26(3B): 2281-7.
    [37] Bujas T, Marusic Z, Peric Balja M, et al. MAGE-A3/4 and NYESO- 1 antigens expression in metastatic esophageal squamous cell carcinoma[J]. Eur J Histochem, 2011, 55(1): e7.
    [38] Akcakanat A, Kanda T, Tanabe T, et al. Heterogeneous expression of GAGE, NY-ESO-1, MAGE-A and SSX proteins in esophageal cancer: Implications for immunotherapy[J]. Int J Cancer, 2006, 11 8(1): 123-8.
    [39] Reynolds SR, Zeleniuch-Jacquotte A, Shapiro RL, et al. Vaccineinduced CD8+ T-cell responses to MAGE-3 correlate with clinical outcome in patients with melanoma[J]. Clin Cancer Res, 2003, 9( 2): 657-62.
    [40] Vantomme V, Dantinne C, Amrani N, et al. Immunologic analysis of a phase Ⅰ/Ⅱ study of vaccination with MAGE-3 protein combined with the AS02B adjuvant in patients with MAGE-3- positive tumors[J]. J Immunother, 2004, 27(2): 124-35.
    [41] Slingluff CL Jr, Petroni GR, Olson W, et al. Helper T-cell responses and clinical activity of a melanoma vaccine with multiple peptides from MAGE and melanocytic differentiation antigens[J]. J Clin Oncol, 2008, 26(30): 4973-80.
    [42] Vansteenkiste J, Zielinski M, Linder A, et al. Adjuvant MAGE-A3 immunotherapy in resected non-small-cell lung cancer: phase II randomized study results[J]. J Clin Oncol, 2013, 31(19): 23 96-403.
    [43] Takahashi N, Ohkuri T, Homma S, et al. First clinical trial of cancer vaccine therapy with artificially synthesized helper/ killerhybrid epitope long peptide of MAGE-A4 cancer antigen[J]. Cancer Sci, 2012, 103(1): 150-3.
    [44] Toh HC, Wang WW, Chia WK, et al. Clinical benefit of allogeneic melanoma cell lysate-pulsed autologous dendritic cell vaccine in mage-positive colorectal cancer patients[J]. Clin Cancer Res, 20 09, 15(24): 7726-36.
    [45] Duffour MT, Chaux P, Lurquin C, et al. A MAGE-A4 peptide presented by HLA-A2 is recognized by cytolytic T lymphocytes[J]. Eur J Immunol, 1999, 29(10): 3329-37.
    [46] Wu ZY, Gao YF, Wu YH, et al. Identification of a novel CD8+ T cell epitope derived from cancer-testis antigen MAGE-4 in oesophageal carcinoma[J]. Scand J Immunol, 2011, 74(6): 561-7.
    [47] Kanaoka S, Yamasaki S, Okino T, et al. Induction of human leukocyte antigen (HLA)-A2-restricted and MAGE-3-genederived peptide-specific cytolytic T lymphocytes using cultured dendritic cells from an HLA-A2 esophageal cancer patient[J]. J Surg Oncol, 1999, 71(1): 16-21.
    [48] Tanaka F, Fujie T, Tahara K, et al. Induction of antitumor cytotoxic T lymphocytes with a MAGE-3-encoded synthetic peptide presented by human leukocytes antigen-A24[J]. Cancer Res, 1997, 57(20): 4465-8.
    [49] Ueda Y, Shimizu K, Itoh T, et al. Induction of peptide-specific immune response in patients with primary malignant melanoma of the esophagus after immunotherapy using dendritic cells pulsed with MAGE peptides[J]. Jpn J Clin Oncol, 2007, 37(2): 140-5.
    [50] Zhang XM, Huang Y, Li ZS, et al. Prediction and analysis of HLA-A2/A24-restricted cytotoxic T-lymphocyte epitopes of the tumor antigen MAGE-n using the artificial neural networks method on NetCTL1.2 Server[J]. Oncol Lett, 2010, 1(6): 1097-100.
计量
  • 文章访问数:  1640
  • HTML全文浏览量:  318
  • PDF下载量:  555
  • 被引次数: 0
出版历程
  • 收稿日期:  2014-05-04
  • 修回日期:  2014-07-30
  • 刊出日期:  2015-06-24

目录

    /

    返回文章
    返回
    x 关闭 永久关闭