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Immune effects of α and β radionuclides in metastatic prostate cancer α和β放射性核素对转移性前列腺癌的免疫效应
IF 12.1 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-08-27 DOI: 10.1038/s41585-024-00924-5
Sapna Lunj, Tim Andrew Davies Smith, Kimberley Jayne Reeves, Fred Currell, Jamie Honeychurch, Peter Hoskin, Ananya Choudhury
External beam radiotherapy is used for radical treatment of organ-confined prostate cancer and to treat lesions in metastatic disease whereas molecular radiotherapy with labelled prostate-specific membrane antigen ligands and radium-223 (223Ra) is indicated for metastatic prostate cancer and has demonstrated substantial improvements in symptom control and overall survival compared with standard-of-care treatment. Prostate cancer is considered an immunologically cold tumour, so limited studies investigating the treatment-induced effects on the immune response have been completed. However, emerging data support the idea that radiotherapy induces an immune response in prostate cancer, but whether the response is an antitumour or pro-tumour response is dependent on the radiotherapy regime and is also cell-line dependent. In vitro data demonstrate that single-dose radiotherapy regimes induce a greater immune-suppressive profile than fractionated regimes; less is known about the immune response induced by molecular radiotherapy agents, but evidence suggests that these agents might induce an immune-suppressive systemic immune response, indicated by increased expression of inhibitory checkpoint molecules such as programmed cell death 1 ligand 1 and 2, and that these changes could be associated with clinical response. Different radiotherapy modalities can induce distinct immune profiles, which can either activate or suppress immune-mediated tumour killing and the current preclinical models used for prostate cancer research are not yet optimal for studying the complexity of the radiotherapy-induced immune response. This Review focusses on what is known about the interactions between conventional radiotherapy and the immune system. The authors discuss how this knowledge can be applied to investigate gaps regarding the immune interactions of molecular radiotherapies.
体外放射治疗用于器官封闭性前列腺癌的根治性治疗和转移性疾病的病灶治疗,而使用标记的前列腺特异性膜抗原配体和镭-223(223Ra)的分子放射治疗则适用于转移性前列腺癌,与常规治疗相比,该疗法在症状控制和总生存率方面有显著改善。前列腺癌被认为是一种免疫功能低下的肿瘤,因此有关治疗对免疫反应影响的研究十分有限。不过,新出现的数据支持放疗诱导前列腺癌免疫反应的观点,但这种反应是抗肿瘤反应还是促肿瘤反应取决于放疗方案,也取决于细胞系。体外数据表明,单剂量放疗方案比分次放疗方案诱导的免疫抑制作用更大;目前对分子放疗药物诱导的免疫反应了解较少,但有证据表明,这些药物可能会诱导免疫抑制性全身免疫反应,表现为抑制性检查点分子(如程序性细胞死亡 1 配体 1 和 2)的表达增加,这些变化可能与临床反应有关。不同的放疗模式可诱导不同的免疫特征,从而激活或抑制免疫介导的肿瘤杀伤作用,而目前用于前列腺癌研究的临床前模型还不是研究放疗诱导免疫反应复杂性的最佳模型。
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引用次数: 0
Field effect and forerunner genes drive bladder cancer initiation 场效应和先驱基因驱动膀胱癌的发生
IF 12.1 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-08-12 DOI: 10.1038/s41585-024-00929-0
Maria Chiara Masone
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引用次数: 0
AI for drug discovery 人工智能促进药物研发
IF 12.1 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-08-09 DOI: 10.1038/s41585-024-00931-6
Louise Lloyd
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引用次数: 0
Utility of PSA screening in transgender women receiving oestrogens 接受雌激素治疗的变性女性接受 PSA 筛查的效用
IF 12.1 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-08-09 DOI: 10.1038/s41585-024-00930-7
Maria Chiara Masone
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引用次数: 0
Urology’s carbon footprint 泌尿外科的碳足迹
IF 12.1 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-08-09 DOI: 10.1038/s41585-024-00934-3
Louise Lloyd
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引用次数: 0
Immunotherapy for penile cancer 阴茎癌免疫疗法
IF 12.1 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-08-09 DOI: 10.1038/s41585-024-00932-5
Louise Lloyd
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引用次数: 0
Single-cell analysis of advanced prostate cancer 晚期前列腺癌的单细胞分析
IF 12.1 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-08-09 DOI: 10.1038/s41585-024-00933-4
Louise Lloyd
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引用次数: 0
Accurate information provided by artificial intelligence 人工智能提供的准确信息。
IF 12.1 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-08-08 DOI: 10.1038/s41585-024-00928-1
Louise Lloyd
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引用次数: 0
Neoadjuvant lutetium PSMA, the TIME and immune response in high-risk localized prostate cancer 高危局部前列腺癌的新辅助卢塞恩 PSMA、TIME 和免疫反应。
IF 12.1 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-08-07 DOI: 10.1038/s41585-024-00913-8
Renu S. Eapen, Scott G. Williams, Sean Macdonald, Simon P. Keam, Nathan Lawrentschuk, Lewis Au, Michael S. Hofman, Declan G. Murphy, Paul J. Neeson
High-risk localized prostate cancer remains a lethal disease with high rates of recurrence, metastases and death, despite attempts at curative local treatment including surgery. Disease recurrence is thought to be a result of failure of local control and occult micrometastases. Neoadjuvant strategies before surgery have been effective in many cancers, but, to date, none has worked in this setting for prostate cancer. Prostate-specific membrane antigen (PSMA)-based theranostics is an exciting and rapidly evolving field in prostate cancer. The novel intravenous radionuclide therapy, [177Lu]Lu-PSMA-617 (lutetium PSMA) has been shown to be effective in treating men with metastatic castration-resistant prostate cancer, targeting cells expressing PSMA throughout the body. When given in a neoadjuvant setting, lutetium PSMA might also improve long-term oncological outcomes in men with high-risk localized disease. A component of radiotherapy is potentially an immunogenic form of cancer cell death. Lutetium PSMA could cause cancer cell death, resulting in release of tumour antigens and induction of a tumour-specific systemic immune response. This targeted radioligand treatment has the potential to treat local and systemic tumour sites by directly targeting cells that express PSMA, but might also act indirectly via this systemic immune response. In selected patients, lutetium PSMA could potentially be combined with systemic immunotherapies to augment the antitumour T cell response, and this might produce long-lasting immunity in prostate cancer. Lutetium PSMA is approved for the treatment of advanced prostate cancer and is being studied in a neoadjuvant setting. The influence of lutetium PSMA on the tumour immune microenvironment is unknown. In selected patients, lutetium PSMA could be used as a stand-alone treatment or in combination with immunotherapy to produce long-lasting antitumour immunity.
尽管尝试了包括手术在内的局部根治性治疗,但高危局部前列腺癌仍然是一种致命疾病,复发率、转移率和死亡率都很高。疾病复发被认为是局部控制失败和隐匿性微转移的结果。手术前的新辅助治疗策略对许多癌症都有疗效,但迄今为止,还没有一种治疗方法对前列腺癌有效。基于前列腺特异性膜抗原(PSMA)的治疗技术是前列腺癌领域一个令人兴奋且发展迅速的领域。新型静脉放射性核素疗法[177Lu]Lu-PSMA-617(镥PSMA)已被证明能有效治疗转移性阉割耐药前列腺癌患者,靶向全身表达PSMA的细胞。如果在新辅助治疗中使用,镥PSMA还能改善高危局部疾病患者的长期肿瘤治疗效果。放疗的一个组成部分是可能导致癌细胞死亡的免疫原性形式。镥PSMA可导致癌细胞死亡,从而释放肿瘤抗原,诱导肿瘤特异性全身免疫反应。这种放射性配体靶向治疗有可能通过直接靶向表达 PSMA 的细胞来治疗局部和全身肿瘤部位,也可能通过这种全身免疫反应间接发挥作用。在选定的患者中,镥PSMA有可能与全身免疫疗法相结合,以增强抗肿瘤T细胞的反应,这可能会对前列腺癌患者产生持久的免疫力。
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引用次数: 0
From foes to friends: rethinking the role of lymph nodes in prostate cancer 从敌人到朋友:重新思考淋巴结在前列腺癌中的作用
IF 12.1 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-08-02 DOI: 10.1038/s41585-024-00912-9
Raghav Gupta, Chandan K. Das, Sujit S. Nair, Adriana Marcela Pedraza-Bermeo, Ali H. Zahalka, Natasha Kyprianou, Nina Bhardwaj, Ashutosh K. Tewari
Clinically localized prostate cancer is often treated with radical prostatectomy combined with pelvic lymph node dissection. Data suggest that lymph node dissection does improve disease staging, but its therapeutic value has often been debated, with few studies showing that lymph node removal directly improves oncological outcomes; however, lymph nodes are an important first site of antigen recognition and immune system activation and the success of many currently used immunological therapies hinges on this dogma. Evidence, particularly in the preclinical setting, has demonstrated that the success of immune checkpoint inhibitors is dampened by the removal of tumour-draining lymph nodes. Thus, whether lymph nodes are truly ‘foes’ or whether they are actually ‘friends’ in oncological care is an important idea to discuss. Pelvic lymph node dissection is performed for staging and to prevent recurrence of prostate cancer; however, immune checkpoint inhibition could be affected by lymph node removal. Here, the authors discuss the possibility that lymph nodes could be ‘friends’ rather than ‘foes’ in prostate cancer treatment.
临床上,局部前列腺癌通常采用根治性前列腺切除术结合盆腔淋巴结清扫术进行治疗。数据表明,淋巴结清扫术确实能改善疾病分期,但其治疗价值却经常受到争议,很少有研究表明淋巴结切除能直接改善肿瘤预后;然而,淋巴结是抗原识别和免疫系统激活的重要第一站,目前使用的许多免疫疗法的成功都有赖于这一信条。有证据表明,尤其是临床前的证据表明,免疫检查点抑制剂的成功会受到切除肿瘤淋巴结的影响。因此,淋巴结在肿瘤治疗中究竟是 "敌人 "还是 "朋友 "是一个值得讨论的重要问题。
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引用次数: 0
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