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Mechanism-based treatment of cancer with immune checkpoint inhibitor therapies.基于机制的免疫检查点抑制剂疗法治疗癌症。
Br J Clin Pharmacol. 2020 Sep;86(9):1690-1702. doi: 10.1111/bcp.14316. Epub 2020 May 12.
2
Cancer immunotherapy resistance based on immune checkpoints inhibitors: Targets, biomarkers, and remedies.基于免疫检查点抑制剂的癌症免疫治疗耐药性：靶点、生物标志物和治疗方法。
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3
Metabolic interventions combined with CTLA-4 and PD-1/PD-L1 blockade for the treatment of tumors: mechanisms and strategies.代谢干预联合 CTLA-4 和 PD-1/PD-L1 阻断治疗肿瘤：机制与策略。
Front Med. 2023 Oct;17(5):805-822. doi: 10.1007/s11684-023-1025-7. Epub 2023 Oct 28.
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Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer.癌症中免疫检查点 PD-L1 和 CTLA-4 的调控机制。
J Exp Clin Cancer Res. 2021 Jun 4;40(1):184. doi: 10.1186/s13046-021-01987-7.
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Immune checkpoints and their inhibition in cancer and infectious diseases.免疫检查点及其在癌症和传染病中的抑制作用。
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Immune Checkpoint Inhibitors.免疫检查点抑制剂
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The Evolving Role of Immune Checkpoint Inhibitors in Cancer Treatment.免疫检查点抑制剂在癌症治疗中不断演变的作用。
Oncologist. 2015 Jul;20(7):812-22. doi: 10.1634/theoncologist.2014-0422. Epub 2015 Jun 11.
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Preserving the CTLA-4 Checkpoint for Safer and More Effective Cancer Immunotherapy.保留 CTLA-4 检查点以实现更安全、更有效的癌症免疫治疗。
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Second- and third-generation drugs for immuno-oncology treatment-The more the better?免疫肿瘤治疗的第二代和第三代药物——越多越好？
Eur J Cancer. 2017 Mar;74:55-72. doi: 10.1016/j.ejca.2017.01.001. Epub 2017 Feb 10.
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A Systematic Review of Immunotherapy in Urologic Cancer: Evolving Roles for Targeting of CTLA-4, PD-1/PD-L1, and HLA-G.免疫疗法在泌尿系统肿瘤中的系统评价：CTLA-4、PD-1/PD-L1 和 HLA-G 靶向作用的不断演变。
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引用本文的文献

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Immunotherapy in the Management of Penile Cancer-A Systematic Review.阴茎癌治疗中的免疫疗法——一项系统评价
Cancers (Basel). 2025 Mar 4;17(5):883. doi: 10.3390/cancers17050883.
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Personalization of Cancer Treatment: Exploring the Role of Chronotherapy in Immune Checkpoint Inhibitor Efficacy.癌症治疗的个性化：探索时辰疗法在免疫检查点抑制剂疗效中的作用
Cancers (Basel). 2025 Feb 21;17(5):732. doi: 10.3390/cancers17050732.
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Immune Checkpoint Inhibitors in the Treatment of Ocular Surface Cancers: A Review.免疫检查点抑制剂在眼表癌治疗中的应用综述
Semin Ophthalmol. 2025 Feb 9:1-11. doi: 10.1080/08820538.2025.2458658.
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Into the Future: Fighting Melanoma with Immunity.展望未来：借助免疫疗法对抗黑色素瘤。
Cancers (Basel). 2024 Nov 29;16(23):4002. doi: 10.3390/cancers16234002.
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Outcomes and Adverse Events in Patients with Cancer after Diagnosis of Immunotherapy-Associated Diabetes Mellitus: A Retrospective Cohort Study.免疫治疗相关糖尿病诊断后癌症患者的结局和不良事件：一项回顾性队列研究
Cancers (Basel). 2024 Apr 25;16(9):1663. doi: 10.3390/cancers16091663.
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Reigniting hope in cancer treatment: the promise and pitfalls of IL-2 and IL-2R targeting strategies.重新点燃癌症治疗的希望：IL-2 和 IL-2R 靶向策略的前景与挑战。
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Demyelinating polyneuropathy combined with brachial plexopathy after nivolumab therapy for hodgkin lymphoma: a case report.尼伏鲁单抗治疗霍奇金淋巴瘤后出现脱髓鞘性多发性神经病合并臂丛神经病：一例报告。
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Immune-related toxicity and soluble profile in patients affected by solid tumors: a network approach.免疫相关毒性与实体瘤患者可溶性谱：网络分析。
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Targeting the secreted RGDKGE collagen fragment reduces PD‑L1 by a proteasome‑dependent mechanism and inhibits tumor growth.靶向分泌型 RGDKGE 胶原蛋白片段通过蛋白酶体依赖性机制降低 PD-L1 并抑制肿瘤生长。
Oncol Rep. 2023 Feb;49(2). doi: 10.3892/or.2023.8481. Epub 2023 Jan 12.
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Comprehensive Multiomic Analysis Identified TUBA1C as a Potential Prognostic Biological Marker of Immune-Related Therapy in Pan-Cancer.全面多组学分析鉴定 TUBA1C 为泛癌免疫相关治疗的潜在预后生物标志物。
Comput Math Methods Med. 2022 Oct 30;2022:9493115. doi: 10.1155/2022/9493115. eCollection 2022.

本文引用的文献

1
Mechanism of resistance to immune checkpoint inhibitors.免疫检查点抑制剂耐药机制。
Cancer Drug Resist. 2019 Jun 19;2(2):178-188. doi: 10.20517/cdr.2018.015. eCollection 2019.
2
Impact of concomitant medication use and immune-related adverse events on response to immune checkpoint inhibitors.伴随用药和免疫相关不良反应对免疫检查点抑制剂应答的影响。
Immunotherapy. 2020 Feb;12(2):141-149. doi: 10.2217/imt-2019-0064. Epub 2020 Feb 17.
3
Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4.新型免疫检查点靶点：超越 PD-1 和 CTLA-4。
Mol Cancer. 2019 Nov 6;18(1):155. doi: 10.1186/s12943-019-1091-2.
4
Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study.帕博利珠单抗单药或联合化疗对比西妥昔单抗联合化疗用于治疗复发性或转移性头颈部鳞状细胞癌（KEYNOTE-048）：一项随机、开放标签、III 期研究。
Lancet. 2019 Nov 23;394(10212):1915-1928. doi: 10.1016/S0140-6736(19)32591-7. Epub 2019 Nov 1.
5
Changing Body Weight-Based Dosing to a Flat Dose for Avelumab in Metastatic Merkel Cell and Advanced Urothelial Carcinoma.将阿维鲁单抗的体重新剂量调整为固定剂量用于转移性 Merkel 细胞癌和晚期尿路上皮癌。
Clin Pharmacol Ther. 2020 Mar;107(3):588-596. doi: 10.1002/cpt.1645. Epub 2019 Nov 18.
6
Immune checkpoint inhibitor combinations: Current efforts and important aspects for success.免疫检查点抑制剂联合治疗：当前的努力和成功的重要方面。
Drug Resist Updat. 2019 Jul;45:13-29. doi: 10.1016/j.drup.2019.07.004. Epub 2019 Jul 29.
7
Five-Year Survival and Correlates Among Patients With Advanced Melanoma, Renal Cell Carcinoma, or Non-Small Cell Lung Cancer Treated With Nivolumab.接受纳武单抗治疗的晚期黑色素瘤、肾细胞癌或非小细胞肺癌患者的五年生存率及相关因素
JAMA Oncol. 2019 Oct 1;5(10):1411-1420. doi: 10.1001/jamaoncol.2019.2187.
8
Role of IDO and TDO in Cancers and Related Diseases and the Therapeutic Implications.吲哚胺 2,3-双加氧酶（IDO）和色氨酸 2,3-双加氧酶（TDO）在癌症及相关疾病中的作用及其治疗意义
J Cancer. 2019 Jun 2;10(12):2771-2782. doi: 10.7150/jca.31727. eCollection 2019.
9
Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252): a phase 3, randomised, double-blind study.依匹单抗联合帕博利珠单抗对比安慰剂联合帕博利珠单抗用于不可切除或转移性黑色素瘤患者（ECHO-301/KEYNOTE-252）：一项 III 期、随机、双盲研究。
Lancet Oncol. 2019 Aug;20(8):1083-1097. doi: 10.1016/S1470-2045(19)30274-8. Epub 2019 Jun 17.
10
Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial.仑伐替尼联合帕博利珠单抗治疗晚期子宫内膜癌患者：一项多中心、开放标签、单臂、2 期临床试验的中期分析。
Lancet Oncol. 2019 May;20(5):711-718. doi: 10.1016/S1470-2045(19)30020-8. Epub 2019 Mar 25.

基于机制的免疫检查点抑制剂疗法治疗癌症。

Mechanism-based treatment of cancer with immune checkpoint inhibitor therapies.

机构信息

Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York.

Department of Pharmacy, Roswell Park Comprehensive Cancer Center, Buffalo, New York.

出版信息

Br J Clin Pharmacol. 2020 Sep;86(9):1690-1702. doi: 10.1111/bcp.14316. Epub 2020 May 12.

DOI:10.1111/bcp.14316
PMID:32323342
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8176998/
Abstract

Immune checkpoints are cell surface molecules that initiate regulatory pathways which have powerful control of CD8 cytolytic T cell activity. Antagonistic and agonistic antibodies engaging these molecules have demonstrated profound impact on immune activation and have entered clinical use for the treatment of a variety of diseases. Over the past decade, antagonistic antibodies known as immune checkpoint inhibitors have become a new pillar of cancer treatment and have reshaped the therapeutic landscape in oncology. These agents differ in their mechanism of action and toxicity profiles compared to more traditional systemic cancer treatments such as chemo- and targeted therapies. This article reviews the pharmacology of this new class of agents.

摘要

免疫检查点是细胞表面分子，可启动对 CD8 细胞毒性 T 细胞活性具有强大控制作用的调节途径。与这些分子结合的拮抗性和激动性抗体已证明对免疫激活具有深远影响，并已用于治疗各种疾病。在过去十年中，被称为免疫检查点抑制剂的拮抗性抗体已成为癌症治疗的新支柱，并重塑了肿瘤学的治疗格局。与更传统的全身癌症治疗（如化疗和靶向治疗）相比，这些药物在作用机制和毒性特征方面有所不同。本文综述了这一类新型药物的药理学。