Next generation of immune checkpoint therapy in cancer: new developments and challenges.
Next generation of immune checkpoint therapy in cancer: new developments and challenges.
复制标题
DOI：
10.1186/s13045-018-0582-8
复制
发表时间：
2018-03-15
影响因子：
28.5
通讯作者：
Lou Y
中科院分区：
文献类型：
--
作者：
Marin-Acevedo JA;Dholaria B;Soyano AE;Knutson KL;Chumsri S;Lou Y
免疫检查点由抑制性和刺激性途径组成，其维持自身耐受性并辅助免疫应答。在癌症中，免疫检查点途径通常被激活以抑制新生的抗肿瘤免疫应答。免疫检查点疗法通过阻断或刺激这些途径起作用，并增强机体对肿瘤的免疫活性。细胞毒性T淋巴细胞相关分子-4（CTLA-4）、程序性细胞死亡受体-1（PD-1）和程序性细胞死亡配体-1（PD-L1）是研究和公认最广泛的抑制性检查点通路。阻断这些途径的药物目前用于各种恶性肿瘤，并已在一部分癌症患者中显示出持久的临床活性。这种方法正在迅速扩展到CTLA-4和PD-1/PD-L1之外。新的抑制途径正在研究中，阻断LAG-3、TIM-3、TIGIT、VISTA或B7/H3的药物也正在研究中。此外，刺激性检查点途径的激动剂如OX 40、ICOS、GITR、4-1BB、CD 40或靶向肿瘤微环境组分的分子如IDO或TLR正在研究中。在这篇文章中，我们对癌症免疫治疗中涉及的免疫检查点途径进行了全面综述，并讨论了它们的机制和目前正在I/II期临床试验中研究的治疗干预措施。我们还回顾了局限性，毒性和挑战，并概述了未来可能的研究方向。
Immune checkpoints consist of inhibitory and stimulatory pathways that maintain self-tolerance and assist with immune response. In cancer, immune checkpoint pathways are often activated to inhibit the nascent anti-tumor immune response. Immune checkpoint therapies act by blocking or stimulating these pathways and enhance the body’s immunological activity against tumors. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1(PD-L1) are the most widely studied and recognized inhibitory checkpoint pathways. Drugs blocking these pathways are currently utilized for a wide variety of malignancies and have demonstrated durable clinical activities in a subset of cancer patients. This approach is rapidly extending beyond CTLA-4 and PD-1/PD-L1. New inhibitory pathways are under investigation, and drugs blocking LAG-3, TIM-3, TIGIT, VISTA, or B7/H3 are being investigated. Furthermore, agonists of stimulatory checkpoint pathways such as OX40, ICOS, GITR, 4-1BB, CD40, or molecules targeting tumor microenvironment components like IDO or TLR are under investigation. In this article, we have provided a comprehensive review of immune checkpoint pathways involved in cancer immunotherapy, and discuss their mechanisms and the therapeutic interventions currently under investigation in phase I/II clinical trials. We also reviewed the limitations, toxicities, and challenges and outline the possible future research directions.
登录
查看更多内容
影响因子：
7.4
作者：
Brignone C;Gutierrez M;Mefti F;Brain E;Jarcau R;Cvitkovic F;Bousetta N;Medioni J;Gligorov J;Grygar C;Marcu M;Triebel F
通讯作者：
Triebel F
T细胞共刺激和共抑制的分子机制。
DOI：
10.1038/nri3405
发表时间：
2013-04
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
50.5
作者：
Champiat, S.;Lambotte, O.;Marabelle, A.
通讯作者：
Marabelle, A.
影响因子：
5.8
作者：
Chester, Cariad;Ambulkar, Siddhant;Kohrt, Holbrook E.
通讯作者：
Kohrt, Holbrook E.
影响因子：
4.1
作者：
de la Torre AN;Contractor S;Castaneda I;Cathcart CS;Razdan D;Klyde D;Kisza P;Gonzales SF;Salazar AM
通讯作者：
Salazar AM