{"title":"Identification of an immunomodulatory lncRNA signature associated with immune cell reprogramming in high-grade glioma.","authors":"Alessandro Canella, Prajwal Rajappa","doi":"10.1038/s41417-025-00919-3","DOIUrl":null,"url":null,"abstract":"<p><p>High-grade gliomas (HGGs) are among the most aggressive brain tumors in pediatric, adolescent, and young adult (AYA) cancer patients, with a median survival of 12-15 months post-diagnosis. Their poor prognosis is driven by a highly immunosuppressive tumor immune microenvironment (TIME), which inhibits cytotoxic immune infiltration and anti-tumor response. This study investigated the involvement of long non-coding RNAs (lncRNAs) in shaping the immune phenotype of HGGs using two murine models: RCAS-PDGFb representing an immunosuppressive TME, and RCAS-BRAF V600E characterized by a signature more consistent with a pro-inflammatory TME. Transcriptomic analysis of tumor-infiltrating immune cells identified distinct lncRNA signatures associated with immunosuppressive and pro-inflammatory TMEs. Single-cell RNA sequencing and spatial transcriptomics supported context-dependent expression of these lncRNAs in high-grade glioma-associated immune cells, such as myeloid, T, and NK cells, and revealed their spatial distribution within the glioblastoma (GBM) TME. Several lncRNAs were enriched at the tumor edge and within necrotic regions in GBM patient samples, correlating with immunosuppression reprogramming and immune evasion mechanisms. These findings highlight specific immunomodulatory lncRNAs as potential players in the immunosuppressive glioma TME, and likely candidates for future studies aimed at developing novel therapeutic strategies to overcome immune suppression and improve clinical outcomes.</p>","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":" ","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer gene therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41417-025-00919-3","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
High-grade gliomas (HGGs) are among the most aggressive brain tumors in pediatric, adolescent, and young adult (AYA) cancer patients, with a median survival of 12-15 months post-diagnosis. Their poor prognosis is driven by a highly immunosuppressive tumor immune microenvironment (TIME), which inhibits cytotoxic immune infiltration and anti-tumor response. This study investigated the involvement of long non-coding RNAs (lncRNAs) in shaping the immune phenotype of HGGs using two murine models: RCAS-PDGFb representing an immunosuppressive TME, and RCAS-BRAF V600E characterized by a signature more consistent with a pro-inflammatory TME. Transcriptomic analysis of tumor-infiltrating immune cells identified distinct lncRNA signatures associated with immunosuppressive and pro-inflammatory TMEs. Single-cell RNA sequencing and spatial transcriptomics supported context-dependent expression of these lncRNAs in high-grade glioma-associated immune cells, such as myeloid, T, and NK cells, and revealed their spatial distribution within the glioblastoma (GBM) TME. Several lncRNAs were enriched at the tumor edge and within necrotic regions in GBM patient samples, correlating with immunosuppression reprogramming and immune evasion mechanisms. These findings highlight specific immunomodulatory lncRNAs as potential players in the immunosuppressive glioma TME, and likely candidates for future studies aimed at developing novel therapeutic strategies to overcome immune suppression and improve clinical outcomes.
期刊介绍:
Cancer Gene Therapy is the essential gene and cellular therapy resource for cancer researchers and clinicians, keeping readers up to date with the latest developments in gene and cellular therapies for cancer. The journal publishes original laboratory and clinical research papers, case reports and review articles. Publication topics include RNAi approaches, drug resistance, hematopoietic progenitor cell gene transfer, cancer stem cells, cellular therapies, homologous recombination, ribozyme technology, antisense technology, tumor immunotherapy and tumor suppressors, translational research, cancer therapy, gene delivery systems (viral and non-viral), anti-gene therapy (antisense, siRNA & ribozymes), apoptosis; mechanisms and therapies, vaccine development, immunology and immunotherapy, DNA synthesis and repair.
Cancer Gene Therapy publishes the results of laboratory investigations, preclinical studies, and clinical trials in the field of gene transfer/gene therapy and cellular therapies as applied to cancer research. Types of articles published include original research articles; case reports; brief communications; review articles in the main fields of drug resistance/sensitivity, gene therapy, cellular therapy, tumor suppressor and anti-oncogene therapy, cytokine/tumor immunotherapy, etc.; industry perspectives; and letters to the editor.