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Creatine uptake promotes dendritic cell activation and enhances antitumor immunity

ABSTRACT:

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, a high-energy metabolite. DCs from CrT knockout mice exhibited impaired activation and a reduced ability to elicit antigen-specific 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.

INSTRUMENT(S): Liquid Chromatography MS - positive - HILIC, Liquid Chromatography MS - negative - HILIC

PROVIDER: MTBLS12797 | MetaboLights | 2026-03-11

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS12797_LC-MS_negative_hilic_metabolite_profiling.txt	Txt
	a_MTBLS12797_LC-MS_positive_hilic_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS12797_LC-MS_hilic_metabolite_profiling_v2_maf.tsv	Tabular
	s_MTBLS12797.txt	Txt

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