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通过靶向主要免疫检查点PD-1、PD-L1和CTLA-4实现癌症治疗的变革

Revolutionization in Cancer Therapeutics via Targeting Major Immune Checkpoints PD-1, PD-L1 and CTLA-4.

作者信息

Pandey Pratibha, Khan Fahad, Qari Huda A, Upadhyay Tarun Kumar, Alkhateeb Abdulhameed F, Oves Mohammad

机构信息

Department of Biotechnology, Noida Institute of Engineering and Technology, Greater Noida 201306, India.

Department of Biological Science, Faculty of Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

出版信息

Pharmaceuticals (Basel). 2022 Mar 9;15(3):335. doi: 10.3390/ph15030335.

Abstract

Numerous research reports have witnessed dramatic advancements in cancer therapeutic approaches through immunotherapy. Blocking immunological checkpoint pathways (mechanisms employed by malignant cells to disguise themselves as normal human body components) has emerged as a viable strategy for developing anticancer immunity. Through the development of effective immune checkpoint inhibitors (ICIs) in multiple carcinomas, advances in cancer immunity have expedited a major breakthrough in cancer therapy. Blocking a variety of ICIs, such as PD-1 (programmed cell death-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) has improved the immune system's efficacy in combating cancer cells. Recent studies also supported the fact that ICIs combined with other potent antitumor candidates, such as angiogenic agents, could be a solid promising chemopreventive therapeutic approach in improving the effectiveness of immune checkpoint inhibitors. Immune checkpoint blockade has aided antiangiogenesis by lowering vascular endothelial growth factor expression and alleviating hypoxia. Our review summarized recent advances and clinical improvements in immune checkpoint blocking tactics, including combinatorial treatment of immunogenic cell death (ICD) inducers with ICIs, which may aid future researchers in creating more effective cancer-fighting strategies.

摘要

众多研究报告见证了免疫疗法在癌症治疗方法上取得的巨大进展。阻断免疫检查点途径(恶性细胞将自身伪装成正常人体成分所采用的机制)已成为发展抗癌免疫力的可行策略。通过在多种癌症中开发有效的免疫检查点抑制剂(ICI),癌症免疫方面的进展加速了癌症治疗的一项重大突破。阻断多种ICI,如程序性细胞死亡蛋白1(PD-1)、程序性细胞死亡配体1(PD-L1)和细胞毒性T淋巴细胞相关蛋白4(CTLA-4),提高了免疫系统对抗癌细胞的功效。最近的研究还支持这样一个事实,即ICI与其他强效抗肿瘤候选药物(如血管生成剂)联合使用,可能是一种极具前景的化学预防治疗方法,可提高免疫检查点抑制剂的有效性。免疫检查点阻断通过降低血管内皮生长因子表达和缓解缺氧来辅助抗血管生成。我们的综述总结了免疫检查点阻断策略的最新进展和临床改进,包括免疫原性细胞死亡(ICD)诱导剂与ICI的联合治疗,这可能有助于未来的研究人员制定更有效的抗癌策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea97/8952773/567881059faf/pharmaceuticals-15-00335-g001.jpg

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