Department of Cancer Biology, University of Wisconsin Carbone Comprehensive Cancer Center, Madison, WI 53705, USA.
Hum Immunol. 2010 May;71(5):496-504. doi: 10.1016/j.humimm.2010.02.007. Epub 2010 Mar 5.
Prostate cancer is a significant cause of morbidity and mortality among men worldwide. The cornerstone treatment for metastatic prostate cancer is androgen deprivation, which has known effects on prostate tissue apoptosis and thymic regrowth. These findings, together with interest in developing immune-based treatments for prostate cancer, lead us to question whether androgen deprivation causes changes in the adaptive immune responses of prostate cancer patients, and whether the timing of changes has implications for the sequencing of immunotherapies in combination with androgen deprivation. Peripheral blood mononuclear cells were obtained from patients before beginning androgen deprivation therapy (ADT) and at several time points thereafter. These cells were analyzed for the frequency of specific lymphocyte populations and their response to stimulation. The development of prostate antigen-specific immune responses was assessed using SEREX (serological identification of antigens by recombinant expression). Patients developed expansion of the naive T-cell compartment persisting over the course of androgen deprivation, together with an increase in effector-cell response to stimulation, and the generation of prostate tissue-associated IgG antibody responses, implying a potential benefit to the use of ADT in combination with prostate cancer-directed immunotherapies. The optimal timing and sequence of androgen deprivation with immune-based therapies awaits future experimental evaluation.
前列腺癌是全球男性发病率和死亡率的重要原因。转移性前列腺癌的基础治疗方法是雄激素剥夺，其对前列腺组织凋亡和胸腺再生有明确作用。这些发现，加上对开发用于前列腺癌的免疫治疗的兴趣，使我们质疑雄激素剥夺是否会导致前列腺癌患者适应性免疫反应发生变化，以及变化的时间是否会影响与雄激素剥夺联合使用的免疫治疗的顺序。我们从开始雄激素剥夺治疗 (ADT) 之前和之后的几个时间点获取患者的外周血单核细胞。分析这些细胞中特定淋巴细胞群的频率及其对刺激的反应。使用 SEREX（通过重组表达进行血清学鉴定抗原）评估前列腺抗原特异性免疫反应的发展。患者在雄激素剥夺过程中持续发展出幼稚 T 细胞区室的扩张，同时对刺激的效应细胞反应增加，并产生与前列腺组织相关的 IgG 抗体反应，这意味着 ADT 联合前列腺癌靶向免疫治疗可能具有潜在益处。雄激素剥夺与免疫治疗联合应用的最佳时机和顺序尚待进一步的实验评估。
