Creatine uptake regulates CD8 T cell antitumor immunity
Di Biase S, Ma X, Wang X, Yu J, Wang YC, Smith DJ, Zhou Y, Li Z, Kim YJ, Clarke N, To A, Yang L
The Journal of experimental medicine · 105 citations
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- Animals
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Independent funding
- Government
- U.S. Department of Health and Human Services
- Government
- National Institutes of Health
- University or hospital
- University of California, Los Angeles
- Government
- National Cancer Institute
- Government
- US Department of Health and Human Services
- Government
- NCI NIH HHS
- University or hospital
- UCLA
- Grants
- U.S. Department of Health and Human Services (T32 CA009056); National Cancer Institute (P30 CA016042); National Institutes of Health (5t32ca009056-47); National Cancer Institute (DP2 CA196335); National Institutes of Health (1dp2ca196335-01); National Cancer Institute (T32-CA009056)
Based on 7 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2019-10-18 · J Exp Med · vol. 216 · issue 12 · pp. 2869–2882
- Publisher
- Rockefeller University Press
- Cited
- 136 citations · more than 95% of similar papers · 3.8× the field average
- Impact
- Top 10% most cited in its field
- References
- 40 works
- Access
- Open access (hybrid journal) · CC-BY
- Research areas
- Cancer, Hypoxia, and Metabolism · Histone Deacetylase Inhibitors Research · Muscle metabolism and nutrition
- Keywords
- Creatine, Immune system, Cytotoxic T cell, CD8, Immunity, T cell, Biology, Cancer research, Internal medicine, Immunology, Endocrinology, Medicine, Biochemistry
- MeSH
- cd8-positive t-lymphocytes, cell line, tumor, animals, mice, knockout, humans, mice, neoplasms, creatine, membrane transport proteins, antigens, neoplasm, lymphocyte activation, gene expression regulation, neoplastic, energy metabolism, models, biological, dietary supplements, immunomodulation, tumor microenvironment
12 authors
From US
- Stefano Di BiaseUniversity of California, Los Angeles
- Xiaoya MaUniversity of California, Los Angeles
- Xi WangUniversity of California, Los Angeles
- Jiaji YuUniversity of California, Los Angeles
- Yu-Chen WangUniversity of California, Los Angeles
- Drake J. SmithUniversity of California, Los Angeles
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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