Serological immune response to cancer testis antigens in patients with pancreatic cancer

Serological immune response to cancer testis antigens in patients with pancreatic cancer
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DOI:
10.1002/ijc.21744
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发表时间:
2006-07-01
影响因子:
6.4
通讯作者:
Renner, Christoph
Renner, Christoph
中科院分区:
医学1区
文献类型:
--
作者:
Wadle, Andreas;Kubuschok, Boris;Renner, Christoph

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血清学筛查方法已经允许在癌症患者中识别大量潜在相关的肿瘤抗原。在这一组中,癌睾丸抗原代表了癌症免疫治疗的有希望的靶点,因为它们在各种人类癌症实体中广泛表达。然而,在胰腺癌中,关于癌睾丸抗原和其他血清学定义的肿瘤抗原的表达模式和血清学反应的数据很少。因此,我们在96例胰腺癌(n = 96)、18例慢性胰腺炎(n = 18)和48例健康供者中研究了针对酵母表面重组表达的11种癌睾丸抗原(SCP-1、GAGE、lag -1a、-1b、CT-7、NY-ESO-1、SSX-1-5)的IgG抗体应答。我们发现14%的患者对SCP-1有抗体反应,但对其他睾丸癌抗原(GAGE, lag -1a,-1b, CT-7, NY-ESO-1, SSX-1-5)无抗体反应。通过RT-PCR、免疫组织化学和Western blot分析,抗体应答与患者原发肿瘤中SCP-1的表达相关。相比之下,在健康供体中没有观察到对癌睾丸抗原的血清学反应。针对SCP-1的体液免疫反应与肿瘤的大小有关,但与其他临床病理参数(如组织学、分期、淋巴结转移的存在、分级、年龄、性别或吉西他滨治疗)无关。总之,在一定比例的胰腺癌患者中存在对癌睾丸抗原SCP-1的抗体反应。这些结果表明,通过ray对肿瘤cDNA表达文库的血清学筛选来鉴定额外的肿瘤抗原是胰腺癌研究的一个有希望的目标。(c) 2006 Wiley-Liss, Inc。
Serological screening approaches have allowed for the identification of a large number of potentially relevant tumor antigens in cancer patients. Within this group, cancer testis antigens represent promising targets for cancer immunotherapy, since they are widely expressed in a variety of human cancer entities. In pancreatic cancer, however, there are only few data available about the expression pattern and serological response to cancer testis antigens and other serological-defined tumor antigens. Therefore, we investigated the IgG antibody response against 11 cancer testis antigens (SCP-1, GAGE, LAGE-1a,-1b, CT-7, NY-ESO-1, SSX-1-5) recombinantly expressed on yeast surface (RAYS) in patients,with pancreatic cancer (n = 96), chronic pancreatitis (n = 18) and healthy donors (n = 48). We found in 14% of all patients antibody responses to SCP-1, but not to other cancer testis antigens (GAGE, LAGE-1a,-1b, CT-7, NY-ESO-1, SSX-1-5). Antibody response correlated with the expression of SCP-1 in the primary tumor of the respective patient as shown by RT-PCR, immunohistochemistry and Western blot. In contrast, no serological response to cancer testis antigens was observed in healthy donors. The humoral immune response against SCP-1 was associated with the size of tumor, but not with other clinico-pathological parameters such as histology, stage, presence of lymph node metastases, grading, age gender or gemcitabine treatment. In conclusion, antibody response to cancer testis antigen SCP-1 is found in a proportion of pancreatic carcinoma patients. These results indicate that identification of additional tumor antigens by serological screening of tumor cDNA expression libraries by RAYS is a promising goal in pancreatic cancer. (c) 2006 Wiley-Liss, Inc.