Immunotherapy: a new treatment paradigm in bladder cancer.
Immunotherapy: a new treatment paradigm in bladder cancer.
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DOI：
10.1097/cco.0000000000000366
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发表时间：
2017-05
影响因子：
3.4
通讯作者：
Apolo AB
中科院分区：
文献类型：
--
作者：
Davarpanah NN;Yuno A;Trepel JB;Apolo AB
T细胞检查点阻断已成为膀胱癌的一种动态免疫疗法。2016年，免疫检查点抑制剂阿特唑珠单抗成为30多年来第一个获准用于转移性尿路上皮癌(MUC)的新药。2017年，nivolumab也被批准用于同样的适应症。本文综述了临床试验中的检查点抑制剂，重点介绍了新的免疫治疗组合，包括突变负荷和新抗原识别在内的预测生物标志物，以及对膀胱癌免疫治疗未来的评估。程序化细胞死亡蛋白1/程序化死亡配体1(PD-1/PD-L1)检查点抑制剂在部分既往治疗和未接受治疗的MUC患者中取得了持久的临床反应。PD-1和细胞毒性T淋巴细胞抗原4(CTLA-4)的联合应用已经成功地提高了多种恶性肿瘤的应答率，许多肿瘤类型的联合研究正在进行中，包括膀胱癌，将T细胞检查点阻断与其他检查点药物和免疫调节治疗相结合。据报道，肿瘤对检查点阻断的强烈反应与肿瘤和肿瘤浸润性免疫细胞上PD-L1的表达以及突变相关新抗原负荷的增加呈正相关，这可能导致预测性生物标记物的发展。最近的临床证据表明，MUC易受T细胞检查点阻断的影响。全球正在努力实现更高的应答率和更持久的缓解，加快免疫疗法的发展，采用联合疗法，并测试新的免疫靶点。
T-cell checkpoint blockade has become a dynamic immunotherapy for bladder cancer. In 2016, atezolizumab, an immune checkpoint inhibitor, became the first new drug approved in metastatic urothelial carcinoma (mUC) in over 30 years. In 2017, nivolumab was also approved for the same indication. This overview of checkpoint inhibitors in clinical trials focuses on novel immunotherapy combinations, predictive biomarkers including mutational load and neoantigen identification, and an evaluation of the future of bladder cancer immunotherapy. Programed cell death protein 1/programed death-ligand 1 (PD-1/PD-L1) checkpoint inhibitors have achieved durable clinical responses in a subset of previously treated and treatment-naïve patients with mUC. The combination of PD-1 and cytotoxic T-lymphocyte antigen 4 (CTLA-4) has successfully improved response rates in multiple malignancies, and combination studies are underway in many tumor types, including bladder cancer, combining T-cell checkpoint blockade with other checkpoint agents and immunomodulatory therapies. Strong tumor responses to checkpoint blockade have been reported to be positively associated with expression of PD-L1 on tumor and tumor-infiltrating immune cells and with increased mutation-associated neoantigen load, which may lead to the development of predictive biomarkers. Recent clinical evidence suggests that mUC is susceptible to T-cell checkpoint blockade. A global effort is underway to achieve higher response rates and more durable remissions, accelerate the development of immunotherapies, employ combination therapies, and test novel immune targets.