Upregulation of RIG-I is Critical for Responsiveness to IFN-α Plus Anti-PD-1 in Colorectal Cancer

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2025-03-21 DOI:10.1002/cam4.70802

Haihang Nie, Shilin Fang, Rui Zhou, Yifan Jia, Jingkai Zhou, Yumei Ning, Yali Yu, Yuntian Hong, Fei Xu, Qiu Zhao, Jiayan Nie, Fan Wang

{"title":"Upregulation of RIG-I is Critical for Responsiveness to IFN-α Plus Anti-PD-1 in Colorectal Cancer","authors":"Haihang Nie, Shilin Fang, Rui Zhou, Yifan Jia, Jingkai Zhou, Yumei Ning, Yali Yu, Yuntian Hong, Fei Xu, Qiu Zhao, Jiayan Nie, Fan Wang","doi":"10.1002/cam4.70802","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Backgrounds</h3>\n \n <p>Immunotherapy is a promising and effective approach that has achieved significant curative effects in colorectal cancer (CRC). Recently, retinoic acid-inducible gene I (RIG-I) has been shown to play a critical role in tumor immunity. However, the correlation between RIG-I and immunotherapy in CRC remains unclear.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>RIG-I expression was measured in CRC and normal samples based on analysis of the public databases, a tissue microarray, and CRC cell lines. The correlation between RIG-I and immune microenvironment was explored using well-established biological algorithms and in vitro and in vivo experiments.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>We discovered that RIG-I expression was downregulated in CRC compared with normal samples. The bioinformatic algorithms indicated that high RIG-I-expressing samples showed a positive correlation with IFN-α response and enrichment of antitumor immune cells, especially CD8+ T cells. Furthermore, knockdown of RIG-I expression efficiently reduced the cell death, STAT1 phosphorylation, and CXCL10/11 expression induced by IFN-α in CRC cells. Finally, an in vivo study showed that the infiltration of CD3+ CD8+ T cells was significantly decreased in the RIG-I knockout group. An animal model further confirmed that the inhibition of tumor growth induced by IFN-α plus anti-PD-1 therapy was dependent on RIG-I expression.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>RIG-I is a promising biomarker for CRC immunotherapy, which provides a novel concept for combinatorial immunotherapy.</p>\n </section>\n </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 6","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926914/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cam4.70802","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Backgrounds

Immunotherapy is a promising and effective approach that has achieved significant curative effects in colorectal cancer (CRC). Recently, retinoic acid-inducible gene I (RIG-I) has been shown to play a critical role in tumor immunity. However, the correlation between RIG-I and immunotherapy in CRC remains unclear.

Methods

RIG-I expression was measured in CRC and normal samples based on analysis of the public databases, a tissue microarray, and CRC cell lines. The correlation between RIG-I and immune microenvironment was explored using well-established biological algorithms and in vitro and in vivo experiments.

Results

We discovered that RIG-I expression was downregulated in CRC compared with normal samples. The bioinformatic algorithms indicated that high RIG-I-expressing samples showed a positive correlation with IFN-α response and enrichment of antitumor immune cells, especially CD8+ T cells. Furthermore, knockdown of RIG-I expression efficiently reduced the cell death, STAT1 phosphorylation, and CXCL10/11 expression induced by IFN-α in CRC cells. Finally, an in vivo study showed that the infiltration of CD3+ CD8+ T cells was significantly decreased in the RIG-I knockout group. An animal model further confirmed that the inhibition of tumor growth induced by IFN-α plus anti-PD-1 therapy was dependent on RIG-I expression.

Conclusion

RIG-I is a promising biomarker for CRC immunotherapy, which provides a novel concept for combinatorial immunotherapy.

Abstract Image

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.