ArticleFrontiers in immunology2023
Creatine supplementation enhances anti-tumor immunity by promoting adenosine triphosphate production in macrophages.
Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 18 citations in OpenAlex.
- Fingerprinting the Metabolic and Lipidomic Landscapes of Pancreatic Ductal Adenocarcinoma with MALDI Imaging.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Guided immunotherapy for residual solid tumor: integrating platelets and CAR T cells to reduce post-surgical recurrence.Biomarker research · 2026Review
- Creatine Supplementation in Preclinical Models Receiving Immune Checkpoint Inhibitor Therapy: A Systematic Review.Cureus · 2026Review
- Article
- From Chronic Inflammation to Cancer: The Role of Trained Immunity in IBD-Associated Colorectal Carcinogenesis.Medical sciences (Basel, Switzerland) · 2026Review
- Effect of supplemental feeding on metabolic profiles and meat quality in yaks: a non-targeted metabolomics approach.Food science of animal resources · 2026Article
- Multi-dimensional immunoprotection of Ganoderma lucidum spore oil in immunosuppressed mice via microbiome-proteome-metabolome network analysis.Scientific reports · 2026Article
- Leveraging glucan-induced trained immunity for the epigenetic and metabolic rewiring of macrophages to enhance colorectal cancer vaccine response.Nature communications · 2026Article
- Ras protein activator-like 3 is a key Ras GTPase-activating protein that protects the survival and anti-tumor activity of CD8Frontiers in immunology · 2026Article
- Metabolomics Plasma Biomarkers Associated with the HRD Phenotype in Ovarian Cancer.Metabolites · 2025Article
- Integrative multi-omics analysisiScience · 2025Article
- Peroxisome proliferator-activated receptor alpha is an essential factor in enhanced macrophage immune function induced by angiotensin-converting enzyme.Cellular & molecular immunology · 2025Article
- It Is Not Just About Storing Energy: The Multifaceted Role of Creatine Metabolism on Cancer Biology and Immunology.International journal of molecular sciences · 2024Review
- The impact of creatine levels on musculoskeletal health in the elderly: a mendelian randomization analysis.BMC musculoskeletal disorders · 2024Article
- Eating for immunity: how diet shapes our defenses.Current opinion in immunology · 2024Review
- Exploring the relationship between creatine supplementation and renal function: insights from Mendelian randomization analysis.Renal failure · 2024Article
- Metabolic Profiling of Cochlear Organoids Identifies α-Ketoglutarate and NADAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Review
- Article
- Reduction in creatine metabolites in macrophages exposed to small molecule analogues of the anti-inflammatory parasitic worm product ES-62.Parasite immunology · 2024Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Creatine is an indispensable organic compound utilized in physiological environments; however, its role in immunity is still poorly understood. Here, we show that creatine supplementation enhances anti-tumor immunity through the functional upregulation of macrophages by increasing adenosine triphosphate (ATP) production. Creatine supplementation significantly suppressed B16-F10-originated tumor growth in mice compared with the control treatment. Under these conditions, intratumor macrophages polarized towards the M1 phenotype rather than the M2 phenotype, and there was an increase in tumor antigen-specific CD8+ T cells in the mice. The cytokine production and antigen-presenting activity in the macrophages were enhanced by creatine supplementation, resulting in a substantial increase in tumor antigen-specific CD8+ T cells. ATP upregulation was achieved through the cytosolic phosphocreatine (PCr) system via extracellular creatine uptake, rather than through glycolysis and mitochondrial oxidative phosphorylation in the macrophages. Blockade of the creatine transporter (CrT) failed to upregulate ATP and enhance the immunological activity of macrophages in creatine supplementation, which also impaired CD8+ T cell activity. Consequently, CrT blockade failed to suppress tumor growth in the creatine-supplemented mice. Thus, creatine is an important nutrient that promotes macrophage function by increasing ATP levels, ultimately contributing to enhanced anti-tumor immunity orchestrated by CD8+ T cells.
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Registered trials
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