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Open AccessArticle

RORα Regulates Cholesterol Metabolism of CD8+ T Cells for Anticancer Immunity

Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Korea
Department of Molecular Bioscience, College of Biomedical Sciences, Kangwon National University, Chuncheon 24341, Korea
Program in Nanoscience and Technology, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Korea
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
Division of Bio-Medical Science & Technology, Korea University of Science and Technology (UST), Daejeon 34113, Korea
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2020, 12(7), 1733;
Received: 18 May 2020 / Revised: 24 June 2020 / Accepted: 26 June 2020 / Published: 29 June 2020
(This article belongs to the Special Issue Mechanism of Immunotherapy in Cancers)
Retinoic acid-related orphan receptor α (RORα) functions as a transcription factor for various biological processes, including circadian rhythm, inflammation, cancer, and lipid metabolism. Here, we demonstrate that RORα is crucial for maintaining cholesterol homeostasis in CD8+ T cells by attenuating NF-κB transcriptional activity. Cholesterol sulfate, the established natural agonist of RORα, exhibits cellular cytotoxicity on, and increased effector responses in, CD8+ T cells. Transcript analysis reveals that the suppression of RORα leads to the upregulation of NF-κB target genes in T cells. Chromatin immunoprecipitation analysis was used to determine the corecruitment of RORα and histone deacetylase (HDAC) on NF-κB target promoters and the subsequent dismissal of coactivators for transcriptional repression. We demonstrate that RORα/HDAC-mediated attenuation of NF-κB signaling controls the balance of cholesterol metabolism in CD8+ T cells, and that therapeutic strategies targeting this epigenetic regulation could be beneficial to the treatment of solid tumors including colon cancers. View Full-Text
Keywords: Cholesterol; CD8+ T cell; RORα; NF-κB Cholesterol; CD8+ T cell; RORα; NF-κB
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Lee, I.K.; Song, H.; Kim, H.; Kim, I.S.; Tran, N.L.; Kim, S.-H.; Oh, S.J.; Lee, J.M. RORα Regulates Cholesterol Metabolism of CD8+ T Cells for Anticancer Immunity. Cancers 2020, 12, 1733.

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