2026-06-05 カリフォルニア大学ロサンゼルス校（UCLA）
◆これまでクレアチンは、がん細胞を直接攻撃するキラーT細胞の活性維持に役立つことが知られていたが、本研究では免疫応答の司令塔である樹状細胞にも重要な役割を果たすことが示された。樹状細胞は腫瘍内の栄養不足環境においてクレアチンの取り込みを増加させ、その機能維持に利用していた。マウスのメラノーマ（悪性黒色腫）モデルでは、クレアチン投与により腫瘍増殖が有意に抑制され、樹状細胞の数や活性化も増加した。樹状細胞は腫瘍抗原を認識してT細胞に提示し、抗腫瘍免疫を誘導するため、その機能強化は既存のがん免疫療法の効果向上につながる可能性がある。
◆研究者らは、クレアチンが免疫細胞のエネルギー代謝を支えることで抗腫瘍免疫を高めると考えており、新たながん治療戦略への応用が期待される。
＜関連情報＞
- https://newsroom.ucla.edu/releases/creatine-may-supercharge-immune-cells-key-to-fighting-cancer
- https://www.cell.com/iscience/fulltext/S2589-0042(26)00811-4
- https://rupress.org/jem/article/216/12/2869/132512/Creatine-uptake-regulates-CD8-T-cell-antitumor
クレアチンの取り込みは樹状細胞の活性化を促進し、抗腫瘍免疫を強化する Creatine uptake promotes dendritic cell activation and enhances antitumor immunity
Elliot Kang ∙ James Elsten-Brown ∙ Yu-Chen Wang ∙ … ∙ Sarah Eckl ∙ Bo Li ∙ Lili Yang
iScience Published: March 21, 2026
DOI:https://doi.org/10.1016/j.isci.2026.115436
Graphical abstract
Highlights
- Dendritic cells upregulate creatine transporter (CrT) upon stimulation
- Creatine supplementation enhances dendritic cell function by modulating ATP balance
- Creatine treatment induces favorable intratumoral dendritic cell phenotypes
Summary
Dendritic cells (DCs) are central regulators of antitumor T cell immunity and are highly sensitive to metabolic cues. However, the therapeutic potential of targeting DC metabolism remains underexplored. Here, we report upregulation of the creatine transporter (CrT; Slc6a8) in intratumoral DCs, which facilitates the cellular uptake of creatine, an energy-storage metabolite. DCs from CrT knockout mice exhibited impaired activation and reduced ability to elicit antigen-specific CD8 T cell responses. Conversely, creatine supplementation enhanced mouse DC activation in vitro and in vivo, and suppressed tumor growth in a syngeneic melanoma model. Notably, creatine uptake similarly boosted the activation and immunostimulatory function of human monocyte-derived DCs. Mechanistically, CrT promotes DC activation by preserving intracellular ATP levels and enhancing energy-dependent inflammatory signaling pathways. Together, these findings uncover a previously unrecognized role for creatine metabolism in regulating DC function and support the use of creatine supplementation as a strategy to augment DC-based cancer immunotherapy.
クレアチンの取り込みはCD8 T細胞の抗腫瘍免疫を調節する Creatine uptake regulates CD8 T cell antitumor immunity
Stefano Di Biase,Xiaoya Ma,Xi Wang,Jiaji Yu,Yu-Chen Wang,Drake J. Smith,Yang Zhou,Zhe Li,Yu Jeong Kim,Nicole Clarke,Angela To,Lili Yang
Journal of Experimental Medicine Published:October 18 2019
DOI:https://doi.org/10.1084/jem.20182044
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.
