肿瘤免疫治疗中的抑制免疫检查点

IF 16.3 1区医学 Q1 IMMUNOLOGY

Science Immunology Pub Date : 2025-09-26 DOI:10.1126/sciimmunol.adv6870

Zhenghai Tang, André Veillette

{"title":"肿瘤免疫治疗中的抑制免疫检查点","authors":"Zhenghai Tang, André Veillette","doi":"10.1126/sciimmunol.adv6870","DOIUrl":null,"url":null,"abstract":"<div >Monoclonal antibodies and other agents that inactivate immune checkpoints like PD-1 and CTLA-4 have been effective against only certain types of cancer and have had highly variable efficacy in patients. These limitations have hastened investigations of additional checkpoints that can serve as therapeutic targets. Nevertheless, no other approach has yet reached the effectiveness of PD-1 and CTLA-4 inactivation. Recent studies have shown that experimental inhibitory immune checkpoints and the drugs targeting them display unexpected or undesirable mechanisms of action or regulation, thus highlighting previously underappreciated complexities of immune checkpoint–based therapies. Understanding these nuances is crucial for developing more effective and safer therapies. This Review explores the intricacies surrounding inhibitory immune checkpoints and offers insights for improved therapeutic strategies in the future.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 111","pages":""},"PeriodicalIF":16.3000,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Inhibitory immune checkpoints in cancer immunotherapy\",\"authors\":\"Zhenghai Tang, André Veillette\",\"doi\":\"10.1126/sciimmunol.adv6870\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div >Monoclonal antibodies and other agents that inactivate immune checkpoints like PD-1 and CTLA-4 have been effective against only certain types of cancer and have had highly variable efficacy in patients. These limitations have hastened investigations of additional checkpoints that can serve as therapeutic targets. Nevertheless, no other approach has yet reached the effectiveness of PD-1 and CTLA-4 inactivation. Recent studies have shown that experimental inhibitory immune checkpoints and the drugs targeting them display unexpected or undesirable mechanisms of action or regulation, thus highlighting previously underappreciated complexities of immune checkpoint–based therapies. Understanding these nuances is crucial for developing more effective and safer therapies. This Review explores the intricacies surrounding inhibitory immune checkpoints and offers insights for improved therapeutic strategies in the future.</div>\",\"PeriodicalId\":21734,\"journal\":{\"name\":\"Science Immunology\",\"volume\":\"10 111\",\"pages\":\"\"},\"PeriodicalIF\":16.3000,\"publicationDate\":\"2025-09-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Science Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.science.org/doi/10.1126/sciimmunol.adv6870\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science Immunology","FirstCategoryId":"3","ListUrlMain":"https://www.science.org/doi/10.1126/sciimmunol.adv6870","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

单克隆抗体和其他灭活免疫检查点（如PD-1和CTLA-4）的药物仅对某些类型的癌症有效，并且对患者的疗效变化很大。这些限制加速了对可作为治疗靶点的额外检查点的研究。然而，目前还没有其他方法达到PD-1和CTLA-4失活的有效性。最近的研究表明，实验性抑制免疫检查点和靶向它们的药物显示出意想不到或不希望的作用或调节机制，从而突出了以前未被重视的基于免疫检查点的治疗的复杂性。了解这些细微差别对于开发更有效、更安全的治疗方法至关重要。本综述探讨了围绕抑制免疫检查点的复杂性，并为未来改进治疗策略提供了见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Inhibitory immune checkpoints in cancer immunotherapy

Monoclonal antibodies and other agents that inactivate immune checkpoints like PD-1 and CTLA-4 have been effective against only certain types of cancer and have had highly variable efficacy in patients. These limitations have hastened investigations of additional checkpoints that can serve as therapeutic targets. Nevertheless, no other approach has yet reached the effectiveness of PD-1 and CTLA-4 inactivation. Recent studies have shown that experimental inhibitory immune checkpoints and the drugs targeting them display unexpected or undesirable mechanisms of action or regulation, thus highlighting previously underappreciated complexities of immune checkpoint–based therapies. Understanding these nuances is crucial for developing more effective and safer therapies. This Review explores the intricacies surrounding inhibitory immune checkpoints and offers insights for improved therapeutic strategies in the future.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Science Immunology Immunology and Microbiology-Immunology

CiteScore

32.90

自引率

2.00%

发文量

183

期刊介绍： Science Immunology is a peer-reviewed journal that publishes original research articles in the field of immunology. The journal encourages the submission of research findings from all areas of immunology, including studies on innate and adaptive immunity, immune cell development and differentiation, immunogenomics, systems immunology, structural immunology, antigen presentation, immunometabolism, and mucosal immunology. Additionally, the journal covers research on immune contributions to health and disease, such as host defense, inflammation, cancer immunology, autoimmunity, allergy, transplantation, and immunodeficiency. Science Immunology maintains the same high-quality standard as other journals in the Science family and aims to facilitate understanding of the immune system by showcasing innovative advances in immunology research from all organisms and model systems, including humans.