Anselmo Da Costa Inês, Rausch Steffen, Kruck Stephan, Todenhöfer Tilman, Stenzl Arnulf, Bedke Jens
a Department of Urology , Eberhard Karls University , Tuebingen , Germany.
Expert Rev Anticancer Ther. 2017 Apr;17(4):357-368. doi: 10.1080/14737140.2017.1292138. Epub 2017 Feb 20.
Historically, renal cell carcinoma (RCC) is considered a chemotherapy-resistant tumor. The cornerstone of systemic therapy included mammalian target of rapamycin (mTOR) inhibitors, endothelial growth factor receptor (VEGFR) and tyrosine kinase inhibitors (TKIs). Currently, a new era is enteres with promising immunotherapeutic treatments, which are becoming commercially available. Areas covered: We provide a comprehensive review using PubMed and ClinicalTrials.gov about the following immunotherapies in RCC: i) vaccine therapy, ii) adoptive T Cell Transfer and CAR T cells, iii) nonspecific immunotherapy - IL-2 (new formulations), iv) Checkpoint inhibitors, v) other checkpoint-molecules. We will also discuss their mechanism of action and toxicity, the importance of developing new patient selection algorithms (immunoprofiling, guidelines updates) and new biomarkers such as PD-1 expression. Expert commentary: Immunotherapy shows promise, and the current tools used in clinical practice, including guidelines, staging-classification and algorithms should be revised and adapted to the new immunotherapeutic drugs. Although immunotherapy in RCC show promising results, more research is needed in parallel to discover biomarkers that enable the prediction of a treatment response and therefore lead to better patient selection.
从历史上看,肾细胞癌(RCC)被认为是一种化疗耐药性肿瘤。全身治疗的基石包括雷帕霉素哺乳动物靶点(mTOR)抑制剂、内皮生长因子受体(VEGFR)和酪氨酸激酶抑制剂(TKIs)。目前,随着有前景的免疫治疗方法进入商业化阶段,一个新时代已然开启。涵盖领域:我们使用PubMed和ClinicalTrials.gov对肾细胞癌的以下免疫疗法进行了全面综述:i)疫苗疗法,ii)过继性T细胞转移和嵌合抗原受体T细胞(CAR T细胞),iii)非特异性免疫疗法——白细胞介素-2(新配方),iv)检查点抑制剂,v)其他检查点分子。我们还将讨论它们的作用机制和毒性、开发新的患者选择算法(免疫分析、指南更新)以及新生物标志物(如PD-1表达)的重要性。专家评论:免疫疗法显示出前景,临床实践中使用的当前工具,包括指南、分期分类和算法,应进行修订并适应新的免疫治疗药物。尽管肾细胞癌的免疫疗法显示出有前景的结果,但仍需要同时开展更多研究以发现能够预测治疗反应从而实现更好的患者选择的生物标志物。