AB043. BRD4 promotes immune escape of glioma cells by upregulating PD-L1 expression
Abstract

AB043. BRD4 promotes immune escape of glioma cells by upregulating PD-L1 expression

Yongsheng Liu, Youxin Zhou

Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China

Correspondence to: Youxin Zhou, MD. Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou 215006, China. Email: zhouyouxin@suda.edu.cn.

Background: Glioblastoma multiforme (GBM) poses significant challenges in treatment due to its aggressive nature and immune escape mechanisms. Despite recent advances in immune checkpoint blockade therapies, GBM prognosis remains poor. The role of bromodomain and extraterminal domain protein 4 (BRD4) in GBM, especially its interaction with immune checkpoints, is not well understood.

Methods: Bioinformatic gene expression and survival analysis for BRD4 was utilized in The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Clone formation assay, Transwell, Cell Counting Kit-8 (CCK8), and wound healing assay were utilized to validate BRD4’s promotion of glioma cell proliferation, invasion, and migration. Chromatin immunoprecipitation (ChIP) assay was conducted to confirm BRD4 binding to the programmed death ligand 1 (PD-L1) promoter. A co-culture model was utilized with activated cluster of differentiation 8 (CD8)+ T cells and glioma cells. GL261 cells with BRD4 short hairpin RNA (shRNA) and/or PD-L1 cDNA were intracranially injected into mice to investigate tumor growth and survival time. Tumor tissue characteristics were analyzed using hematoxylin-eosin (H&E) and immunohistochemistry (IHC) staining and immune cell infiltration were assessed by flow cytometry.

Results: Bioinformatics analyses reveal elevated BRD4 expression in high-grade gliomas, correlating with poor patient survival. In vitro studies confirm that BRD4 promotes proliferation, invasion, and migration in GBM cells. BRD4 is a regulator of PD-L1 at the transcriptional level, implying its involvement in GBM’s immune escape mechanisms. Co-culture experiments with CD8+ T cells demonstrate that BRD4 inhibition enhances tumor cell apoptosis. In vivo studies indicate that BRD4 knockout reduces immunosuppression, improves prognosis. Simultaneous manipulation of BRD4 and PD-L1 levels provides insights into their intertwined roles in shaping the immune landscape of GBM.

Conclusions: BRD4 has the capability to regulate the growth of glioblastoma and enhance immune suppression by promoting PD-L1 expression. Targeting BRD4 represents a promising direction for future research and treatment.

Keywords: Bromodomain and extraterminal domain protein 4 (BRD4); programmed death ligand 1 (PD-L1); glioma; immune escape, apoptosis

Acknowledgments

Funding: The present study was funded by the National Key Research and Development Program of China (No. 2021YFF0704805).

Footnote

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://cco.amegroups.com/article/view/10.21037/cco-24-ab043/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and approved by the Ethics Committee of Soochow University (approval No. SUDA20221206H03). Because of the retrospective nature of the research, the requirement for informed consent was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the noncommercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

Cite this abstract as: Liu Y, Zhou Y. AB043. BRD4 promotes immune escape of glioma cells by upregulating PD-L1 expression. Chin Clin Oncol 2024;13(Suppl 1):AB043. doi: 10.21037/cco-24-ab043

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