한빛사논문
- 조회310
Amit Sharma 1,2, Garima Sharma 1,3,17, Zhen Gao 4,17, Ke Li 4, Mutong Li 4, Menglin Wu 4, Chan Johng Kim 1,5, Yingjia Chen 6, Anupam Gautam 7,8, Hong Bae Choi 9, Jin Kim 10, Jung-Myun Kwak 10, Sin Man Lam 11,12, Guanghou Shui 11,13, Sandip Paul 14, Yongqiang Feng 6, Keunsoo Kang 15, Sin-Hyeog Im 1,3,16,* and Dipayan Rudra 1,4,*
1Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea.
2Innovation Research Center for Biofuture Technology (B-IRC), Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea.
3ImmmunoBiome Inc, Pohang 37673, Republic of Korea.
4School of Life Science & Technology, ShanghaiTech University, Shanghai 201210, China.
5Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
6Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA.
7Institute for Bioinformatics and Medical Informatics, University of Tübingen, Sand 14, Tübingen 72076, Germany.
8International Max Planck Research School “From Molecules to Organisms”, Max Planck Institute for Biology Tübingen, Max-Planck-Ring 5, Tübingen 72076, Germany.
9Daehang Hospital, Seoul 06699, Republic of Korea.
10Department of Surgery, Korea University College of Medicine, Seoul 02841, Republic of Korea.
11State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology Chinese Academy of Sciences, Beijing 100101, China.
12Lipidall Technologies Company Limited, Changzhou 213022 Jiangsu Province, China.
13University of Chinese Academy of Sciences, Beijing 100101, China.
14Center for Health Science and Technology, JIS Institute of Advanced Studies and Research, JIS University, Kolkata 700091, India.
15Department of Microbiology, College of Natural Sciences, Dankook University, Cheonan 31116, Republic of Korea.
16Institute for Convergence Research and Education in Advanced Technology, Yonsei University, Seoul 03722, Republic of Korea.
17These authors contributed equally: Garima Sharma, Zhen Gao.
*Corresponding authors: correspondence to Sin-Hyeog Im or Dipayan Rudra
Abstract
Regulatory T cells (Tregs) establish dominant immune tolerance but obstruct tumor immune surveillance, warranting context-specific mechanistic insights into the functions of tumor-infiltrating Tregs (TIL-Tregs). We show that enhanced posttranslational O-linked N-acetylglucosamine modification (O-GlcNAcylation) of cellular factors is a molecular feature that promotes a tumor-specific gene expression signature and distinguishes TIL-Tregs from their systemic counterparts. We found that altered glucose utilization through the glucose transporter Glut3 is a major facilitator of this process. Treg-specific deletion of Glut3 abrogates tumor immune tolerance, while steady-state immune homeostasis remains largely unaffected in mice. Furthermore, by employing mouse tumor models and human clinical data, we identified the NF-κB subunit c-Rel as one such factor that, through Glut3-dependent O-GlcNAcylation, functionally orchestrates gene expression in Tregs at tumor sites. Together, these results not only identify immunometabolic alterations and molecular events contributing to fundamental aspects of Treg biology, specifically at tumor sites but also reveal tumor-specific cellular properties that can aid in the development of Treg-targeted cancer immunotherapies.
논문정보
- Research article
- 2024년 10월 (BRIC 등록일 2024-10-29)
- 국내(교신)+국외 연구진
관련 보도자료
- Bio통신원
- 2024. 11. 12
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