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Potentiating prostate cancer immunotherapy with oncolytic viruses
Nature Reviews Urology ( IF 15.3 ) Pub Date : 2018-02-13 , DOI: 10.1038/nrurol.2018.10
Patrick Lee , Shashi Gujar

The clinical effectiveness of immunotherapies for prostate cancer remains subpar compared with that for other cancers. The goal of most immunotherapies is the activation of immune effectors, such as T cells and natural killer cells, as the presence of these activated mediators positively correlates with patient outcomes. Clinical evidence shows that prostate cancer is immunogenic, accessible to the immune system, and can be targeted by antitumour immune responses. However, owing to the detrimental effects of prostate-cancer-associated immunosuppression, even the newest immunotherapeutic approaches fail to initiate the clinically desired antitumour immune reaction. Oncolytic viruses, originally used for their preferential cancer-killing activity, are now being recognized for their ability to overturn cancer-associated immune evasion and promote otherwise absent antitumour immunity. This oncolytic-virus-induced subversion of tumour-associated immunosuppression can potentiate the effectiveness of current immunotherapeutics, including immune checkpoint inhibitors (for example, antibodies against programmed cell death protein 1 (PD1), programmed cell death 1 ligand 1 (PDL1), and cytotoxic T lymphocyte antigen 4 (CTLA4)) and chemotherapeutics that induce immunogenic cell death (for example, doxorubicin and oxaliplatin). Importantly, oncolytic-virus-induced antitumour immunity targets existing prostate cancer cells and also establishes long-term protection against future relapse. Hence, the strategic use of oncolytic viruses as monotherapies or in combination with current immunotherapies might result in the next breakthrough in prostate cancer immunotherapy.



中文翻译:

溶瘤病毒增强前列腺癌免疫治疗

与其他癌症相比,针对前列腺癌的免疫疗法的临床疗效仍未达到理想水平。大多数免疫疗法的目标是激活免疫效应物,例如T细胞和自然杀伤细胞,因为这些激活的介导物的存在与患者预后成正相关。临床证据表明,前列腺癌具有免疫原性,可以进入免疫系统,并且可以通过抗肿瘤免疫反应靶向。然而,由于前列腺癌相关免疫抑制的有害作用,即使是最新的免疫治疗方法也不能引发临床上所需的抗肿瘤免疫反应。溶瘤病毒最初是出于其优先的杀癌活性而使用的,现已被公认为具有推翻与癌症相关的免疫逃避和促进原本缺乏抗肿瘤免疫能力的能力。这种溶瘤病毒诱导的与肿瘤相关的免疫抑制的颠覆可以增强当前免疫治疗的有效性,包括免疫检查点抑制剂(例如,针对程序性细胞死亡蛋白1(PD1),程序性细胞死亡1配体1(PDL1)的抗体,以及细胞毒性T淋巴细胞抗原4(CTLA4))和诱导免疫原性细胞死亡的化学疗法(例如,阿霉素和奥沙利铂)。重要的是,溶瘤病毒诱导的抗肿瘤免疫作用以现有的前列腺癌细胞为目标,并建立了防止将来复发的长期保护措施。因此,

更新日期:2018-02-13
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