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膀胱癌的免疫疗法:当前方法与未来展望

Immunotherapy in Bladder Cancer: Current Methods and Future Perspectives.

作者信息

Wołącewicz Mikołaj, Hrynkiewicz Rafał, Grywalska Ewelina, Suchojad Tomasz, Leksowski Tomasz, Roliński Jacek, Niedźwiedzka-Rystwej Paulina

机构信息

Institute of Biology, University of Szczecin, 71-412 Szczecin, Poland.

Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, 20-093 Lublin, Poland.

出版信息

Cancers (Basel). 2020 May 7;12(5):1181. doi: 10.3390/cancers12051181.

Abstract

Bladder cancer is one of the most significant genitourinary cancer, causing high morbidity and mortality in a great number of patients. Over the years, various treatment methods for this type of cancer have been developed. The most common is the highly efficient method using Bacillus Calmette-Guerin, giving a successful effect in a high percentage of patients. However, due to the genetic instability of bladder cancer, together with individual needs of patients, the search for different therapy methods is ongoing. Immune checkpoints are cell surface molecules influencing the immune response and decreasing the strength of the immune response. Among those checkpoints, the PD-1 (programmed cell death protein-1)/PD-L1 (programmed cell death protein ligand 1) inhibitors aim at blocking those molecules, which results in T cell activation, and in bladder cancer the use of Atezolizumab, Avelumab, Durvalumab, Nivolumab, and Pembrolizumab has been described. The inhibition of another pivotal immune checkpoint, CTLA-4 (cytotoxic T cell antigen), may result in the mobilization of the immune system against bladder cancer and, among anti-CTLA-4 antibodies, the use of Ipilimumab and Tremelimumab has been discussed. Moreover, several different approaches to successful bladder cancer treatment exists, such as the use of ganciclovir and mTOR (mammalian target of rapamycin) kinase inhibitors, IL-12 (interleukin-12) and COX-2 (cyclooxygenase-2). The use of gene therapies and the disruption of different signaling pathways are currently being investigated. Research suggests that the combination of several methods increases treatment efficiency and the positive outcome in individual.

摘要

膀胱癌是最重要的泌尿生殖系统癌症之一,在大量患者中导致高发病率和高死亡率。多年来,已经开发出针对这种癌症的各种治疗方法。最常见的是使用卡介苗的高效方法,在高比例的患者中取得了成功效果。然而,由于膀胱癌的基因不稳定性以及患者的个体需求,对不同治疗方法的探索仍在进行中。免疫检查点是影响免疫反应并降低免疫反应强度的细胞表面分子。在这些检查点中,PD-1(程序性细胞死亡蛋白1)/PD-L1(程序性细胞死亡蛋白配体1)抑制剂旨在阻断这些分子,从而导致T细胞活化,并且在膀胱癌中已经描述了使用阿特珠单抗、阿维鲁单抗、度伐鲁单抗、纳武单抗和派姆单抗。抑制另一个关键的免疫检查点CTLA-4(细胞毒性T细胞抗原)可能会动员免疫系统对抗膀胱癌,并且在抗CTLA-4抗体中,已经讨论了使用伊匹单抗和曲美木单抗。此外,还存在几种成功治疗膀胱癌的不同方法,例如使用更昔洛韦和mTOR(雷帕霉素靶蛋白)激酶抑制剂、IL-12(白细胞介素-12)和COX-2(环氧化酶-2)。目前正在研究基因疗法的使用以及不同信号通路的破坏。研究表明,几种方法的联合使用可提高治疗效率并使个体获得更好的治疗结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ae5/7281703/5c46cb7ffbd9/cancers-12-01181-g001.jpg

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