前列腺酸性磷酸酶--结肠癌主动免疫治疗新靶点

Prostatic acid phosphatase:new immunotherapeutic target of colon adenocarcinoma

目的探讨前列腺酸性磷酸酶(PAP)作为结肠癌主动免疫治疗新靶点的可能性。方法分别用RT-PCR方法和Western blot方法检测结肠癌细胞系中PAPmRNA和PAP蛋白的表达水平;免疫组织化学方法检测结肠癌肿瘤组织中的PAP蛋白的表达水平。利用PAP表位肽对结肠癌患者的PBMCs进行体外诱导,ELISA法检测PAP特异性IFN-γ分泌水平;51Cr释放法检测CTLs的细胞毒活性。结果3种结肠癌细胞(colo201,colo 205和colo 320)表达PAPmRNA和PAP蛋白,结肠癌组织中PAP呈阳性表达。从3/5个结肠癌患者的PBMCs中诱导出PAP多肽特异性CTLs,CTLs的细胞毒活性依赖于CD8+的T淋巴细胞。结论PAP可能成为结肠癌特异性免疫治疗的新靶点。

Objective To study the expression of prostatic acid phosphatase （PAP）, a prostate-related antigen, in colon adenocarcinoma cell or tissues, to investigate the possibility of PAP as a new immunotherapeutic target of colon adenocarcinoma. Methods 5 colon adenocareinoma cell lines were examined for their PAP expression at mRNA and protein levels by RT-PCR and Western blot analysis, respectively. The PAP expression in colon cancer tissues was also examined by immunohistochemical staining. The PBMCs of HLA-A24 ＋ colon cancer patients were stimulated with a PAP peptide in vitro. The PAP-specific IFN-γ？ was measured by ELISA. The cytotoxicities of CTLs were examined by 51Cr release assay. Results 3 kinds of colon cancer cells （ colo 201,205, and 320） as well as cancer tissues were found to be positive for PAP at both the mRNA and protein levels. PAP-specific CTLs were induced from 3 of 5 colon cancer patients. Their cytotoxicity against HLA-A24 ＋ colon cancer cells was dependent on PAP peptide-specific and CD8 ＋ T cells. Conclusions PAP could be a target molecule in specific immunotherapy for patients with colon cancer.