{"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}
引用次数: 0
Abstract
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.
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.