University of Wisconsin Carbone Comprehensive Cancer Center, Madison, Wisconsin, USA.
Prostate. 2011 Feb 1;71(2):134-46. doi: 10.1002/pros.21229.
An important focus of tumor immunotherapy has been the identification of appropriate antigenic targets. Serum-based screening approaches have led to the discovery of hundreds of tumor-associated antigens recognized by IgG. Our efforts to identify immunologically recognized proteins in prostate cancer have yielded a multitude of antigens; however, prioritizing these antigens as targets for evaluation in immunotherapies has been challenging. In this report, we set out to determine whether the evaluation of multiple antigenic targets would allow the identification of a subset of antigens that are common immunologic targets in patients with prostate cancer.
Using a phage immunoblot approach, we evaluated IgG responses in patients with prostate cancer (n = 126), patients with chronic prostatitis (n = 45), and men without prostate disease (n = 53).
We found that patients with prostate cancer or prostatitis have IgG specific for multiple common antigens. A subset of 23 proteins was identified to which IgG were detected in 38% of patients with prostate cancer and 33% patients with prostatitis versus 6% of controls (P < 0.001 and P = 0.003, respectively). Responses to multiple members were not higher in patients with advanced disease, suggesting antibody immune responses occur early in the natural history of cancer progression.
These findings suggest an association between inflammatory conditions of the prostate and prostate cancer, and suggest that IgG responses to a panel of commonly recognized prostate antigens could be potentially used in the identification of patients at risk for prostate cancer or as a tool to identify immune responses elicited to prostate tissue.
肿瘤免疫治疗的一个重要重点是确定合适的抗原靶标。基于血清的筛选方法已经导致了数百种 IgG 识别的肿瘤相关抗原的发现。我们在前列腺癌中识别免疫识别蛋白的努力产生了许多抗原;然而,将这些抗原作为免疫治疗评估的目标进行优先排序具有挑战性。在本报告中,我们旨在确定评估多个抗原靶标是否可以确定一组在前列腺癌患者中是常见免疫靶标的抗原。
使用噬菌体免疫印迹方法,我们评估了 126 例前列腺癌患者、45 例慢性前列腺炎患者和 53 例无前列腺疾病男性的 IgG 反应。
我们发现前列腺癌或前列腺炎患者具有针对多种常见抗原的 IgG 特异性。鉴定出 23 种蛋白质亚组,其中 38%的前列腺癌患者和 33%的前列腺炎患者 IgG 检测到这些蛋白质,而对照组为 6%(P<0.001 和 P=0.003)。在晚期疾病患者中,对多种成员的反应并没有更高,这表明抗体免疫反应发生在癌症进展的自然史的早期。
这些发现表明前列腺的炎症状况与前列腺癌之间存在关联,并表明对一组常见识别的前列腺抗原的 IgG 反应可潜在地用于识别前列腺癌风险患者或作为识别针对前列腺组织引发的免疫反应的工具。