Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cancer J. 2013 Jan-Feb;19(1):50-8. doi: 10.1097/PPO.0b013e31828160a9.
Immunotherapy has emerged as a viable therapeutic option for patients with prostate cancer. There are multiple potential strategies that use the immune system, including therapeutic cancer vaccines that are designed to stimulate immune cells to target antigens expressed by cancer cells. Sipuleucel-T is a vaccine currently approved for the treatment of minimally symptomatic metastatic prostate cancer, whereas the vaccine PSA-TRICOM and the immune-checkpoint inhibitor ipilimumab are in phase III testing. Although there are no short-term changes in disease progression or available biomarkers to assess response, these agents appear to improve survival. One hypothesis suggests that this apparent paradox can be explained by the growth-moderating effects of these treatments, which do not cause tumor size to diminish, but rather stall or slow their growth rate over time. For this reason, the use of immunotherapy earlier in the disease process is being investigated. Another approach is to block immune-regulatory mechanisms mediated by the molecules cytotoxic T lymphocyte antigen 4 and programmed cell death protein 1. Additional future strategies will combine immunotherapy with other standard therapies, potentially enhancing the latter's clinical impact and thereby improving both time to progression and overall survival due to the combined effects of both treatments. Prospective trials are currently evaluating these hypotheses and will ultimately serve to optimize immunotherapy in the treatment of prostate cancer.
免疫疗法已成为前列腺癌患者的一种可行治疗选择。有多种潜在的策略利用免疫系统，包括旨在刺激免疫细胞靶向癌细胞表达的抗原的治疗性癌症疫苗。Sipuleucel-T 是一种目前批准用于治疗有轻微症状的转移性前列腺癌的疫苗，而疫苗 PSA-TRICOM 和免疫检查点抑制剂 ipilimumab 正在进行 III 期试验。尽管没有疾病进展的短期变化或可用的生物标志物来评估反应，但这些药物似乎确实能提高生存率。一种假设认为，这种明显的悖论可以用这些治疗方法的生长调节作用来解释，这些治疗方法不会导致肿瘤缩小，而是随着时间的推移使肿瘤的生长速度停滞或减缓。出于这个原因，正在研究在疾病过程的早期使用免疫疗法。另一种方法是阻断细胞毒性 T 淋巴细胞抗原 4 和程序性细胞死亡蛋白 1 介导的免疫调节机制。未来的其他策略将把免疫疗法与其他标准疗法结合起来，可能会增强后者的临床影响，从而提高进展时间和总生存率，因为两种治疗方法的联合作用。目前正在进行前瞻性试验来评估这些假设，最终将有助于优化免疫疗法在前列腺癌治疗中的应用。
