Quinn David I, Shore Neal D, Egawa Shin, Gerritsen Winald R, Fizazi Karim
Division of Medical Oncology, University of Southern California Norris Comprehensive Cancer, Los Angeles, CA.
Carolina Urologic Research Center, Myrtle Beach, SC.
Urol Oncol. 2015 May;33(5):245-60. doi: 10.1016/j.urolonc.2014.10.009. Epub 2015 Jan 7.
The approval of sipuleucel-T in conjunction with data from other immunotherapeutic trials for prostate cancer and other solid tumors demonstrates the potential of harnessing the patients' immune system for long-term survival. Thus, a range of therapeutic approaches are under evaluation. This review describes the rationale for immunotherapy for prostate cancer, summarizes the approaches under evaluation, and discusses sequencing options for immunotherapy in the current treatment paradigm.
References for this review were identified through searches of PubMed with the search terms "prostate cancer," "immune system," "vaccine," "immunotherapy," and "T cells." Articles were also identified through searches of the authors' own files. The final reference list was generated based on originality and relevance.
The immune system can recognize and respond to prostate tumor antigens, effected through tumor-associated antigens and tumor infiltration of immune effector cells. However, evidence also suggests that prostate tumors are adept at escaping immunological recognition, thus hypothesizing multiple therapeutic strategies. Therapeutic approaches could include vaccination and modulation of T-cell function via the blockade of checkpoint receptors such as cytotoxic T-lymphocyte antigen-4 and programmed death 1. In phase III trials, sipuleucel-T improved overall survival for an M1 patient population with castration-resistant prostate cancer and ipilimumab also did so when given after radiotherapy in a subset of better risk patients. In randomized phase II trials, prostate-specific antigen-TRICOM improved overall survival and tasquinimod improved progression-free survival.
Although immunotherapy has the potential to affect advanced prostate cancer, additional research is needed to (1) identify predictive or surrogate markers of activity, (2) understand which agents are clinically effective alone or in combination with other therapies, and (3) define the optimal timing for an immunotherapy to achieve maximal benefit.
西妥昔单抗的获批以及其他前列腺癌和其他实体瘤免疫治疗试验的数据表明，利用患者的免疫系统实现长期生存具有潜力。因此，一系列治疗方法正在评估中。本综述描述了前列腺癌免疫治疗的基本原理，总结了正在评估的方法，并讨论了当前治疗模式下免疫治疗的序贯选择。
通过使用“前列腺癌”“免疫系统”“疫苗”“免疫治疗”和“T细胞”等检索词在PubMed上进行检索，确定了本综述的参考文献。还通过检索作者自己的文件确定了文章。最终的参考文献列表是根据原创性和相关性生成的。
免疫系统可以识别前列腺肿瘤抗原并做出反应，这是通过肿瘤相关抗原和免疫效应细胞的肿瘤浸润实现的。然而，证据也表明前列腺肿瘤善于逃避免疫识别，因此提出了多种治疗策略。治疗方法可能包括疫苗接种以及通过阻断细胞毒性T淋巴细胞抗原4和程序性死亡1等检查点受体来调节T细胞功能。在III期试验中，西妥昔单抗改善了去势抵抗性前列腺癌M1患者群体的总生存期，在一部分风险较低的患者中，伊匹单抗在放疗后使用时也有同样效果。在随机II期试验中，前列腺特异性抗原-TRICOM改善了总生存期，他喹莫德改善了无进展生存期。
尽管免疫治疗有可能影响晚期前列腺癌，但仍需要进一步研究以（1）确定活性的预测或替代标志物，（2）了解哪些药物单独或与其他疗法联合使用具有临床疗效，以及（3）确定免疫治疗获得最大益处的最佳时机。
