尽管针对编程死亡配体1和其受体的新型免疫检查点抑制剂已显示出对尿路上皮和肾细胞癌的适度反应，但前列腺癌患者的反应率仍然很低。目前尚未解决使用新型免疫治疗的患者的亚最优结果背后的因素。我们进行了一项非系统的协作叙述性综述，以突出最近的进展，以及导致泌尿生殖（GU）癌症抗肿瘤适应性免疫的关键调节因子的当前知识状态。此外，我们讨论了与三种癌症类型之一独特或具有重叠的临床相关性的治疗前和治疗后免疫学事件的发现。免疫功能下降是导致接受传统和新型免疫治疗的患者表现出亚最优结果的主要因素之一。与GU癌症中低响应相关的其他肿瘤免疫生物学方面包括总体肿瘤突变负荷，特定肿瘤抑制基因/DNA损伤修复基因（KDM6A、PTEN、STAG2、TP53、ATM和BRCA2）的突变以及多种功能状态的适应性免疫细胞的丰富程度及其在肿瘤免疫微环境中的时空定位。了解这些机制可能会导致预测和预测生物标志物（如免疫细胞浸润剖面和第三淋巴结结构（TLSs）），这些生物标志物与新型免疫治疗方法的性质有关，从而导致可变临床结果。实施更新的免疫监测技术和改进的临床前模型系统将增强我们对与免疫治疗反应性的差异贡献的宿主和肿瘤内在因素的了解。尽管在对肿瘤免疫景观中动态和静态适应性免疫元素的理解方面取得了巨大进展，但仍存在一些知识空白。因此，全面掌握的知识将导致精准免疫疗法、改进的药物序列和治疗反应。我们进行了一个多样化的领域专家的协作审查，研究了癌细胞与患者免疫系统之间的事件和交流，这些事件和交流与新型免疫治疗的反应相关。在治疗前后的肿瘤内在和宿主相关的免疫变化不断更新的理解将有助于发现免疫治疗反应的有希望的标志物，以及开发用于管理泌尿生殖系统癌症的独特治疗方法。 2023年 The Author(s) 版权所有，由 Elsevier B.V. 发布。保留所有权利。

While urothelial and renal cell cancers have exhibited modest responses to novel immune checkpoint inhibitors targeting the programmed death ligand 1 and its receptor, response rates in patients with prostate cancer have remained poor. The factors underlying suboptimal outcomes observed in patients treated with novel immunotherapies are still to be resolved.To review the literature and describe the key adaptive immune physiological events associated with cancer progression and therapeutic response in genitourinary (GU) cancers.We performed a nonsystematic, collaborative narrative review to highlight recent advancements leading to the current state of knowledge on the critical mediators of antitumor adaptive immunity to GU cancers. Further, we discuss the findings on the pre- and post-treatment immunological events that either are unique to each of the three cancer types or exhibit overlapping clinical associations.Aging-associated immune function decline is a major factor underlying poor outcomes observed in patients treated with both conventional and novel immunotherapies. Other cancer immunobiological aspects associated with suboptimal responses in GU cancers include the overall tumor mutational burden, mutations in specific tumor suppressor/DNA damage repair genes (KDM6A, PTEN, STAG2, TP53, ATM, and BRCA2), and abundance of multiple functional states of adaptive immune cells and their spatiotemporal localization within the tumor immune microenvironment. Understanding these mechanisms may potentially lead to the development of prognostic and predictive biomarkers such as immune cell infiltration profiles and tertiary lymphoid structures (TLSs) that associate with variable clinical outcomes depending on the nature of the novel immunotherapeutic approach. Implementation of newer immune-monitoring technologies and improved preclinical modeling systems will augment our understanding of the host and tumor intrinsic factors contributing to the variability of responses to immunotherapies.Despite the tremendous progress made in the understanding of dynamic and static adaptive immune elements within the tumor immune landscape, several knowledge gaps remain. A comprehensive knowledge thus gained will lead to precision immunotherapy, improved drug sequencing, and a therapeutic response.We performed a collaborative review by a diverse group of experts in the field to examine our understanding of the events and crosstalk between cancer cells and the patient's immune system that are associated with responses to novel immunotherapies. An evolving understanding of tumor-intrinsic and host-related immune alterations, both before and after therapy, will aid in the discovery of promising markers of responses to immunotherapy as well as the development of unique therapeutic approaches for the management of genitourinary cancers.Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.