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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1471388
This article is part of the Research Topic Molecular and Immune Influences in the Progression of Gliomas Vol II View all articles

Profiling hypoxia signaling reveals a lncRNA signature contributing to immunosuppression in high-grade glioma

Provisionally accepted
Qingyu Liang Qingyu Liang 1*Jingcheng Xu Jingcheng Xu 1Xinqiao Li Xinqiao Li 1Xue Li Xue Li 1Jianghua Shi Jianghua Shi 1Chunmi Wei Chunmi Wei 2
  • 1 The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
  • 2 Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Region, China

The final, formatted version of the article will be published soon.

    Background: Hypoxic conditions in glioma are linked to tumor aggressiveness, poor prognosis, and treatment resistance. Long non-coding RNAs (lncRNAs) play key roles in the hypoxic and immune microenvironment of cancers, but their link to hypoxia-induced immunosuppression in high-grade glioma (HGG) is not well-studied.Methods: Gene expression profiles from TCGA and CGGA, along with clinical and genomic data, were analyzed. Bioinformatics methods including Consensus Clustering, Pearson correlation, and Cox regression analyses were used. Cell proliferation was assessed using cell counting kit-8 and colony formation assays. Glioma-macrophage interactions were evaluated using a co-culture model.Results: Hypoxia subtype clustering showed hypoxic stress correlates with worse HGG prognosis.Eight hypoxia-related lncRNAs (AP000695.4, OSMR-AS1, AC078883.3, RP11-545E17.3, LINC01057, LINC01503, TP73-AS1, and LINC00672) with prognostic value were identified, forming a risk signature that separated patients into distinct prognostic groups. Multivariate Cox regression confirmed the signature as an independent prognostic factor. High-risk patients had greater hypoxia, leading to an immunosuppressive environment and immunotherapy resistance via tumor-associated macrophages (TAMs). TP73-AS1 significantly influenced hypoxia-induced TAM infiltration and M2 polarization.We profiled hypoxic stress in HGG and developed an 8-lncRNA hypoxia-related signature predicting patient survival and immunotherapy response, emphasizing its role in hypoxia-induced immunosuppression.

    Keywords: high-grade glioma, hypoxia, lncRNA, prognosis, Immunotherapy

    Received: 27 Jul 2024; Accepted: 13 Sep 2024.

    Copyright: © 2024 Liang, Xu, Li, Li, Shi and Wei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Qingyu Liang, The First Affiliated Hospital of China Medical University, Shenyang, 110000, Liaoning Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.