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Open AccessArticle

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

1
Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Korea
2
Department of Molecular Bioscience, College of Biomedical Sciences, Kangwon National University, Chuncheon 24341, Korea
3
Program in Nanoscience and Technology, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Korea
4
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
5
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; https://doi.org/10.3390/cancers12071733
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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MDPI and ACS Style

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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