Hartmann Tanja B, Mattern Eva, Wiedemann Nicole, van Doorn Remco, Willemze Rein, Niikura Takako, Hildenbrand Ralf, Schadendorf Dirk, Eichmüller Stefan B
German Cancer Research Center, Skin Cancer Unit, Heidelberg, Germany.
Exp Dermatol. 2008 Apr;17(4):324-34. doi: 10.1111/j.1600-0625.2007.00637.x. Epub 2007 Nov 2.
The knowledge of tumor-associated antigens is required for most types of immunotherapy and can substantially facilitate diagnosis. To identify potential tumor-associated genes expressed in cutaneous T-cell lymphoma (CTCL), we used three complementary strategies: antigens which elicit a humoral immune response in CTCL patients were detected by serological analysis of a recombinant cDNA expression library. cDNAs differentially expressed in CTCL but not peripheral blood monocytes were identified by comparative cDNA hybridization and suppression subtractive hybridization. We identified 43 genes selectively expressed by CTCL cells, that have not yet been described in the context of CTCL development, but most of which had been reported to be associated with cancer. Expression analysis by database mining and subsequently RT-PCR on selected clones confirmed their selective expression in CTCL tissues. Serological tests showed that 15 clones were recognized by sera of CTCL patients but not of healthy donors. Analysis of serological tests for 11 clones using serum antibody detection array (SADA) and 100 sera of controls and CTCL patients each revealed up to 5% reactive sera in the tumor group. The expression pattern of the detected clones and their immunogenicity demonstrates that they might be relevant for the understanding of CTCL and suggests particularly three clones, HD-CL-41 (DRAK2), HD-CL-49 (nudC) and HD-CL-12 (ZNF195) for further analysis with respect to their prognostic and therapeutic value for CTCL.
大多数类型的免疫疗法都需要了解肿瘤相关抗原,这能极大地促进诊断。为了鉴定皮肤T细胞淋巴瘤(CTCL)中表达的潜在肿瘤相关基因,我们采用了三种互补策略:通过重组cDNA表达文库的血清学分析来检测在CTCL患者中引发体液免疫反应的抗原。通过比较cDNA杂交和抑制性消减杂交来鉴定在CTCL中差异表达但在外周血单核细胞中不表达的cDNA。我们鉴定出43个由CTCL细胞选择性表达的基因,这些基因在CTCL的发展背景下尚未被描述,但其中大多数已被报道与癌症相关。通过数据库挖掘进行表达分析,随后对选定克隆进行逆转录聚合酶链反应(RT-PCR),证实了它们在CTCL组织中的选择性表达。血清学检测表明,15个克隆能被CTCL患者的血清识别,但不能被健康供体的血清识别。使用血清抗体检测阵列(SADA)对11个克隆以及分别对100份对照和CTCL患者的血清进行血清学检测分析,结果显示肿瘤组中反应性血清高达5%。所检测克隆的表达模式及其免疫原性表明,它们可能与理解CTCL相关,特别提示三个克隆,即HD-CL-41(DRAK2)、HD-CL-49(nudC)和HD-CL-12(ZNF195),需进一步分析它们对CTCL的预后和治疗价值。