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Creatine uptake regulates CD8 T cell antitumor immunity.

Authors
  • Di Biase, Stefano1
  • Ma, Xiaoya1
  • Wang, Xi1
  • Yu, Jiaji1
  • Wang, Yu-Chen1
  • Smith, Drake J1
  • Zhou, Yang1
  • Li, Zhe1
  • Kim, Yu Jeong1
  • Clarke, Nicole1
  • To, Angela1
  • Yang, Lili2, 3, 4, 5
  • 1 Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA.
  • 2 Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA [email protected]
  • 3 Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA.
  • 4 Jonsson Comprehensive Cancer Center, the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
  • 5 Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA.
Type
Published Article
Journal
Journal of Experimental Medicine
Publisher
The Rockefeller University Press
Publication Date
Dec 02, 2019
Volume
216
Issue
12
Pages
2869–2882
Identifiers
DOI: 10.1084/jem.20182044
PMID: 31628186
Source
Medline
Language
English
License
Unknown

Abstract

T cells demand massive energy to combat cancer; however, the metabolic regulators controlling antitumor T cell immunity have just begun to be unveiled. When studying nutrient usage of tumor-infiltrating immune cells in mice, we detected a sharp increase of the expression of a CrT (Slc6a8) gene, which encodes a surface transporter controlling the uptake of creatine into a cell. Using CrT knockout mice, we showed that creatine uptake deficiency severely impaired antitumor T cell immunity. Supplementing creatine to WT mice significantly suppressed tumor growth in multiple mouse tumor models, and the combination of creatine supplementation with a PD-1/PD-L1 blockade treatment showed synergistic tumor suppression efficacy. We further demonstrated that creatine acts as a "molecular battery" conserving bioenergy to power T cell activities. Therefore, our results have identified creatine as an important metabolic regulator controlling antitumor T cell immunity, underscoring the potential of creatine supplementation to improve T cell-based cancer immunotherapies. © 2019 Di Biase et al.

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