von Rundstedt Friedrich-Carl, Necchi Andrea
Department of Urology, Jena University Hospital, Jena, Germany.
Department of Medical Oncology, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.
Transl Androl Urol. 2017 Dec;6(6):1111-1116. doi: 10.21037/tau.2017.11.11.
Immunotherapy in urothelial cancer is a quickly evolving field as new agents are being investigated in multiple clinical trials and various clinical settings. The purpose of this review is to provide an insight into the mechanism of these treatments, potential targets to evaluate treatment response and to give an update on the current status of clinical trials. Urothelial cancer is a polyclonal disease with a substantial tumor heterogeneity and a high mutational load which may be beneficial as this may trigger a stronger T-cell mediated immune response. PD-1 expression has been shown to correlate with stage, grade, progression and poorer survival but it appears challenging to be utilized as a predictor for treatment response in urothelial cancer. Another important concept is immune cell (IC) infiltration, which is a reflection of the activated immune response within the target tissue. Marker genes may represent signaling pathways involved in T-cell recognition and lysis of T-cells. The complexity of the tumor and host interaction requires multiple concepts to be integrated into a future model to assess treatment response. We have evaluated multiple biomarker approaches currently investigated in clinical trials in urothelial cancer.
随着多种新型药物在多项临床试验和不同临床环境中接受研究，尿路上皮癌的免疫治疗是一个快速发展的领域。本综述的目的是深入探讨这些治疗方法的机制、评估治疗反应的潜在靶点，并介绍临床试验的当前进展。尿路上皮癌是一种多克隆疾病，具有显著的肿瘤异质性和高突变负荷，这可能是有益的，因为这可能引发更强的T细胞介导的免疫反应。PD-1表达已被证明与分期、分级、进展和较差的生存率相关，但在尿路上皮癌中用作治疗反应的预测指标似乎具有挑战性。另一个重要概念是免疫细胞（IC）浸润，它反映了靶组织内激活的免疫反应。标记基因可能代表参与T细胞识别和T细胞裂解的信号通路。肿瘤与宿主相互作用的复杂性需要将多个概念整合到一个未来模型中，以评估治疗反应。我们评估了目前在尿路上皮癌临床试验中研究的多种生物标志物方法。
