Phenotypic insights into genetic risk factors for immune-related adverse events in cancer immunotherapy.

IF 4.6 2区 医学 Q2 IMMUNOLOGY Cancer Immunology, Immunotherapy Pub Date : 2024-11-02 DOI:10.1007/s00262-024-03854-8
Haochuan Ma, Dili Song, Haibo Zhang, Taidong Li, Xing Jin
{"title":"Phenotypic insights into genetic risk factors for immune-related adverse events in cancer immunotherapy.","authors":"Haochuan Ma, Dili Song, Haibo Zhang, Taidong Li, Xing Jin","doi":"10.1007/s00262-024-03854-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Immune-related adverse events (irAEs) pose substantial challenges in the realm of cancer immunotherapy, frequently affecting treatment efficacy and patient safety. To address the urgent need for identifying risk factors associated with irAEs, we conducted a comprehensive phenotype-wide Mendelian randomization analysis (MR-PheWAS).</p><p><strong>Methods: </strong>Utilizing publicly accessible genome-wide association study (GWAS) data, this investigation evaluated the impact of over 5000 exposure variables on susceptibility to irAEs using univariate Mendelian randomization (MR). We categorized these correlations and further explored potential mechanisms by which associated traits might influence irAEs through multivariate MR.</p><p><strong>Results: </strong>MR-PheWAS identified numerous risk factors for irAEs, encompassing both previously documented and novel associations. Specifically, we identified 105 traits with probable causal relationships to all-grade irAEs and 119 traits with suggestive associations. For high-grade irAEs, we categorized 122 traits as probably associated and 141 as suggestively associated. Notably, multivariate MR analyses uncovered intricate interactions, particularly highlighting how diabetes impacts all-grade irAEs through mediators such as body mass index and sex hormone-binding globulin.</p><p><strong>Conclusions: </strong>This study has not only identified new risk factors for irAEs but also confirmed several well-established ones. Further investigation is crucial to validate and assess these identified risk factors within clinical trials. A mechanistic understanding of these causal factors is essential for improving the management and prevention of irAEs.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531409/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Immunology, Immunotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00262-024-03854-8","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Immune-related adverse events (irAEs) pose substantial challenges in the realm of cancer immunotherapy, frequently affecting treatment efficacy and patient safety. To address the urgent need for identifying risk factors associated with irAEs, we conducted a comprehensive phenotype-wide Mendelian randomization analysis (MR-PheWAS).

Methods: Utilizing publicly accessible genome-wide association study (GWAS) data, this investigation evaluated the impact of over 5000 exposure variables on susceptibility to irAEs using univariate Mendelian randomization (MR). We categorized these correlations and further explored potential mechanisms by which associated traits might influence irAEs through multivariate MR.

Results: MR-PheWAS identified numerous risk factors for irAEs, encompassing both previously documented and novel associations. Specifically, we identified 105 traits with probable causal relationships to all-grade irAEs and 119 traits with suggestive associations. For high-grade irAEs, we categorized 122 traits as probably associated and 141 as suggestively associated. Notably, multivariate MR analyses uncovered intricate interactions, particularly highlighting how diabetes impacts all-grade irAEs through mediators such as body mass index and sex hormone-binding globulin.

Conclusions: This study has not only identified new risk factors for irAEs but also confirmed several well-established ones. Further investigation is crucial to validate and assess these identified risk factors within clinical trials. A mechanistic understanding of these causal factors is essential for improving the management and prevention of irAEs.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
癌症免疫疗法中免疫相关不良事件遗传风险因素的表型研究。
背景:免疫相关不良事件(irAEs)给癌症免疫疗法领域带来了巨大挑战,经常影响治疗效果和患者安全。为了满足确定与irAEs相关的风险因素的迫切需要,我们进行了一项全面的全表型孟德尔随机分析(MR-PheWAS):本研究利用公开的全基因组关联研究(GWAS)数据,采用单变量孟德尔随机分析法(MR)评估了 5000 多个暴露变量对虹膜AEs易感性的影响。我们对这些相关性进行了分类,并通过多变量 MR 进一步探讨了相关性状可能影响虹膜急性损伤的潜在机制:结果:MR-PheWAS 发现了许多虹膜睫状体异常的风险因素,其中既有先前记录的相关因素,也有新发现的相关因素。具体来说,我们发现了 105 个特征与所有等级的虹膜急性心肌梗死可能存在因果关系,119 个特征与虹膜急性心肌梗死有提示性关联。对于高级别虹膜急性心动过速,我们将 122 个性状归类为可能相关,141 个性状归类为提示相关。值得注意的是,多变量磁共振分析发现了错综复杂的相互作用,特别强调了糖尿病如何通过体重指数和性激素结合球蛋白等介导因素影响所有等级的虹膜睫状体异常:这项研究不仅发现了新的虹膜AEs风险因素,还证实了几个已经确立的风险因素。进一步的调查对于在临床试验中验证和评估这些已确定的风险因素至关重要。从机理上理解这些致病因素对于改善虹膜急性心动过速的管理和预防至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
10.50
自引率
1.70%
发文量
207
审稿时长
1 months
期刊介绍: Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
期刊最新文献
Efficacy, safety, and biomarker analysis of TACE combined with lenvatinib plus sintilimab in unresectable hepatocellular carcinoma: a real-world study. Dendritic cell maturation is induced by p53-armed oncolytic adenovirus via tumor-derived exosomes enhancing systemic antitumor immunity. Breaking the shield of solid tumors: a combined approach for enhanced efficacy of CAR-T cells. Uncovering the role of tumor cGAS expression in predicting response to PD-1/L1 inhibitors in non-small cell lung cancer. Combination of ataxia telangiectasia and Rad3-related inhibition with ablative radiotherapy remodels the tumor microenvironment and enhances immunotherapy response in lung cancer.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1