| 廖国祥,董 爽.泌尿系统恶性肿瘤免疫检查点阻断治疗的进展[J].肿瘤学杂志,2017,23(2):140-144. |
| 泌尿系统恶性肿瘤免疫检查点阻断治疗的进展 |
| Advances in Immune Checkpoint Blockade Therapy for Urinary System Cancer |
| 投稿时间：2016-08-05 |
| DOI：10.11735/j.issn.1671-170X.2017.02.B013 |
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| 中文关键词: 泌尿系统肿瘤 免疫检查点 |
| 英文关键词:urinary system cancer immune checkpoint |
| 基金项目: |
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| 中文摘要: |
| 摘 要：在肿瘤微环境中，免疫检查点分子过表达会抑制肿瘤特异性T细胞的免疫活性，促进肿瘤的进展。靶向检查点的抗体通过阻断受体—配体相互作用，可以恢复T细胞的抗肿瘤免疫活性。对内分泌治疗抵抗的前列腺癌，CTLA-4抗体易普利姆玛（ipilimumab）单药的Ⅲ期试验中，总体结果为阴性。然而，在预后特征良好的亚组患者，可显著改善总体生存率。在2015~2016年，FDA批准纳武单抗（nivolumab）治疗抗血管治疗后的晚期RCC患者；阿特朱单抗（atezolizumab）治疗转移性尿路上皮癌患者。而且也报道了avelumab（PD-L1抑制剂）和派姆单抗（pembrolizumab）治疗泌尿系统癌症的数据。尽管存在一些差异，在转移性尿路上皮癌铂类治疗后，反应率均优于历史上的细胞毒化疗。此外，PD-L1高表达的肿瘤患者反应率接近30%，而且比化疗有更好的耐受性，3或4度毒性发生率小于15%。也有研究结果鼓励新的免疫疗法联合，与传统的抗癌药物联合治疗的临床试验。然而，也不是在每一个癌症患者都有反应。因此，根据免疫检查点阻断生物机制的科学认识，需要预计单药治疗和联合治疗的生物标志物，并提供早期治疗反应指标。 |
| 英文摘要: |
| Abstract：Over-expression of immune checkpoint molecules in tumor microenvironment inhibits the activity of tumor-specific T cells and promotes tumor progression. Checkpoints-targeted antibodies can restore the antitumor activity of T cells by blocking the receptor-ligand interactions. The clinical trial of CTLA-4 antibody ipilimumab monotherapy showed negative results for endocrinotherapy-resistant prostate cancer；however，for subgroups of prostate cancer with good prognostic features it can significantly improve overall survival. US FDA approved nivolumab for advanced renal cell carcinoma(RCC) patients after anti-angiogenic therapy and atezolizumab(PD-L1 inhibitor) for metastatic urothelial cancer in 2015~2016. It is also reported data about PD-L1 inhibitors avelumab and pembrolizumab for urinary system cancer；although there are some discrepancies，their response rates seem to be superior to cytotoxic chemotherapy for metastatic urothelial cancer after platinum-based therapy. In addition，the response rate in patients with positive expression of PD-L1 is nearly 30% with better tolerance. The results in clinical trials are encouraged for new immune therapy combined with conventional anti-cancer drugs. Based on the biological mechanisms of immune checkpoint block，it is important to find biomarkers for monotherapy or combination therapy and to provide early indicators of therapeutic response. |
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