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免疫疗法在泌尿系统癌症中的作用。

The role of immunotherapy in urological cancers.

机构信息

Department of Urology, University of Health Sciences, Derince Training and Research Hospital, Kocaeli.

Department of Urology, School of Medicine, Kocaeli University.

出版信息

Arch Ital Urol Androl. 2024 May 30;96(2):12307. doi: 10.4081/aiua.2024.12307.

Abstract

Immunotherapy is defined as a therapeutic approach that targets or manipulates the immune system. A deeper understanding of the cellular and molecular composition of the tumour environment, as well as the mechanisms controlling the immune system, has made possible the development and clinical investigation of many innovative cancer therapies. Historically, immunotherapy has played an essential role in treating urologic malignancies, while in the modern era, the development of immune checkpoint inhibitors (ICIs) has been critical to urology. Urothelial carcinoma is a common type of cancer in the genitourinary system, and treatment strategies in this area are constantly evolving. Intravesical and systemic immunotherapeutic agents have begun to be used increasingly frequently in treating urothelial carcinoma. These agents increase the anti-tumour response by affecting the body's defence mechanisms. Immunotherapeutic agents used in urothelial carcinoma include various options such as BCG, interferon, anti-PD-1 (pembrolizumab, nivolumab) and anti-PD-L1 (atezolizumab, avelumab, durvalumab). Renal cell carcinoma (RCC) has been known for many years as a tumour with unique sensitivity to immunotherapies. The recent emergence of ICIs that block PD-1/PD-L1 (pembrolizumab, nivolumab, atezolizumab) or CTLA4 (ipilimumab) signalling pathways has reestablished systemic immunotherapy as central to the treatment of advanced RCC. In light of randomized clinical trials conducted with increasing interest in the application of immunotherapies in the adjuvant setting, combination therapies (nivolumab/ipilimumab, nivolumab/cabozantinib, pembrolizumab/ axitinib, pembrolizumab/lenvantinib) have become the standard first-line treatment of metastatic RCC. Prostate cancer is in the immunologically "cold" tumour category; on the contrary, in recent years, immunotherapeutic agents have come to the fore as an essential area in the treatment of this disease. Especially in the treatment of castration-resistant prostate cancer, immunotherapeutic agents constitute an alternative treatment method besides androgen deprivation therapy and chemotherapy. Ipilimumab, nivolumab, pembrolizumab, atezolizumab, and Sipuleucel T (Vaccine-based) are promising alternative treatment options. Considering ongoing randomized clinical trials, immunotherapeutic agents promise to transform the uro-oncology field significantly. In this review, we aimed to summarize the role of immunotherapy in urothelial, renal and prostate cancer in the light of randomized clinical trials.

摘要

免疫疗法被定义为一种靶向或操纵免疫系统的治疗方法。对肿瘤环境的细胞和分子组成以及控制免疫系统的机制有了更深入的了解,使得许多创新的癌症疗法得以开发和临床研究。历史上,免疫疗法在治疗泌尿系统恶性肿瘤方面发挥了重要作用,而在现代,免疫检查点抑制剂 (ICI) 的发展对泌尿科至关重要。尿路上皮癌是泌尿系统常见的癌症类型,该领域的治疗策略不断发展。膀胱内和全身免疫治疗药物已开始越来越频繁地用于治疗尿路上皮癌。这些药物通过影响机体的防御机制来增强抗肿瘤反应。用于尿路上皮癌的免疫治疗药物包括卡介苗、干扰素、抗 PD-1(pembrolizumab、nivolumab)和抗 PD-L1(atezolizumab、avelumab、durvalumab)等多种选择。肾细胞癌 (RCC) 多年来一直被认为是对免疫疗法具有独特敏感性的肿瘤。最近出现的阻断 PD-1/PD-L1(pembrolizumab、nivolumab、atezolizumab)或 CTLA4(ipilimumab)信号通路的 ICI 重新确立了全身免疫疗法作为治疗晚期 RCC 的核心地位。鉴于越来越多的临床试验对免疫疗法在辅助治疗中的应用进行了随机临床试验,联合治疗(nivolumab/ipilimumab、nivolumab/cabozantinib、pembrolizumab/axitinib、pembrolizumab/lenvantinib)已成为转移性 RCC 的标准一线治疗。前列腺癌属于免疫“冷”肿瘤范畴;相反,近年来,免疫治疗药物已成为治疗这种疾病的一个重要领域。特别是在治疗去势抵抗性前列腺癌方面,免疫治疗药物是除雄激素剥夺疗法和化疗之外的一种替代治疗方法。Ipilimumab、nivolumab、pembrolizumab、atezolizumab 和 Sipuleucel T(基于疫苗)是有前途的替代治疗选择。考虑到正在进行的随机临床试验,免疫治疗药物有望显著改变泌尿肿瘤学领域。在这篇综述中,我们旨在根据随机临床试验总结免疫疗法在尿路上皮癌、肾癌和前列腺癌中的作用。

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