Olson Brian M, McNeel Douglas G
Department of Oncology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Prostate. 2007 Dec 1;67(16):1729-39. doi: 10.1002/pros.20652.
The androgen receptor (AR) is a steroid hormone receptor that is an essential regulator of prostate development, and the primary molecular target for the treatment of metastatic prostate cancer. In this report, we evaluated whether patients with prostate cancer have pre-existing immune responses specific for the AR as evidence that the AR also might be pursued as an immunological target antigen.
The detection of auto-antibodies specific for the AR in patient sera was evaluated by ELISA and Western blotting. Peripheral blood mononuclear cells were analyzed for the presence of AR-specific T-cells, as measured by T-cell proliferation, interferon gamma (IFNgamma) and interleukin-10 secretion.
We found that a significantly higher frequency of prostate cancer patients have AR LBD-specific antibody responses than do healthy male volunteers [18/105 cancer patients (17.1%) vs. 0/41 healthy volunteers, P = 0.0049], and that these responses were present regardless of the patients' disease stage [8/46 organ-confined prostate cancer patients (17.4%), 3/22 metastatic androgen-dependent patients (13.6%), and 7/37 metastatic, androgen-independent patients (18.9%)]. These antibodies were pre-dominantly of the IgG isotype, and furthermore of the IgG(2) sub-isotype. In addition, we found that patients with antibody responses also had concurrent antigen-specific CD4+ and CD8+ T-cell proliferation and IFNgamma secretion when compared to patients without antibody responses.
These data demonstrate that some patients with prostate cancer have pre-existing humoral and cellular immune responses specific for the AR, suggesting that tolerance against the AR is not absolute and that the AR may be a potential immunotherapeutic target antigen.
雄激素受体（AR）是一种类固醇激素受体，是前列腺发育的关键调节因子，也是转移性前列腺癌治疗的主要分子靶点。在本报告中，我们评估了前列腺癌患者是否存在针对AR的预先存在的免疫反应，以此作为AR也可能被作为免疫靶点抗原的证据。
通过酶联免疫吸附测定（ELISA）和蛋白质印迹法评估患者血清中针对AR的自身抗体的检测。通过T细胞增殖、干扰素γ（IFNγ）和白细胞介素-10分泌来分析外周血单个核细胞中AR特异性T细胞的存在情况。
我们发现，前列腺癌患者中AR配体结合域（LBD）特异性抗体反应的频率显著高于健康男性志愿者[105例癌症患者中有18例（17.1%），而41例健康志愿者中为0例，P = 0.0049]，并且无论患者的疾病阶段如何，这些反应均存在[46例局限性前列腺癌患者中有8例（17.4%），22例转移性雄激素依赖性患者中有3例（13.6%），37例转移性雄激素非依赖性患者中有7例（18.9%）]。这些抗体主要为IgG同种型，此外为IgG(2)亚同种型。此外，我们发现与无抗体反应的患者相比，有抗体反应的患者同时存在抗原特异性CD4 +和CD8 + T细胞增殖以及IFNγ分泌。
这些数据表明，一些前列腺癌患者存在针对AR的预先存在的体液免疫和细胞免疫反应，这表明对AR的耐受性并非绝对，并且AR可能是潜在的免疫治疗靶点抗原。
