ArticleNature communications2021
The folate cycle enzyme MTHFD2 induces cancer immune evasion through PD-L1 up-regulation.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed, 185 citations in OpenAlex.
- A systematic transcriptomic atlas and predictive framework for metabolite-driven T cell state transitions.iScience · 2026Article
- A five-gene TAM and MYCN signature predicts prognosis and identifies MTHFD2 as a therapeutic target in neuroblastoma.Discover oncology · 2026Article
- O-GlcNAcylation: the metabolic-immune translator in tumor evolution and treatment.Molecular medicine (Cambridge, Mass.) · 2026Review
- RBMX promotes colorectal liver metastasis by stabilizing MTHFD2 mRNA to regulate redox homeostasis.Cellular and molecular life sciences : CMLS · 2026Article
- Complement C5a/C5aR1 pathway facilitates glioblastoma progression via fostering glioma stem cell-macrophage symbiosis.Journal of neuroinflammation · 2026Article
- NSUN2/m5C/TPI1 axis promotes glycolysis and immune evasion in breast cancer.Journal of translational medicine · 2026Article
- MTHFD2: a promising metabolic checkpoint for diseases.Journal of translational medicine · 2026Review
- Targeting the noncanonical function of metabolic enzyme PHGDH in driving PD-L1 expression and cancer immune evasion.Cell reports. Medicine · 2026Article
- The oncogenic control of nucleotide synthesis.Oncogenesis · 2026Review
- Investigating the oncogenic potential of MTHFD2 in oral squamous cell carcinoma.Journal of cancer research and clinical oncology · 2026Article
- O-GlcNAcylation of UGDH regulates its activity and remodels the extracellular matrix to facilitate tumor growth.Cell death and differentiation · 2026Article
- Astragaloside IV represses the immune evasion and acidic microenvironment of oral squamous cell carcinoma.Cellular & molecular biology letters · 2026Article
- Targeting metabolic-epigenetic-immune axis in cancer: molecular mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- SOX4-STAT6-MTHFD2 axis drives hepatocellular carcinoma progression and treatment resistance.Cell death & disease · 2026Article
- Cancer-Associated Fibroblasts in Gastrointestinal Cancer Metastasis: Mechanisms and Emerging Therapeutic Strategies.Drug design, development and therapy · 2026Review
- O-GlcNAcylation at the tumor-immune interface: a metabolic post-translational code driving immune evasion and therapy resistance in cancer.Frontiers in immunology · 2026Review
- One-carbon metabolism in cancer immunity: T-cell fitness, epigenetic programming, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Recent advances in novel targeting mechanisms for colorectal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Association Between Mefox and Prevalence of COPD: Evidence from NHANES 2011-2020.Healthcare (Basel, Switzerland) · 2025Article
- Non-canonical dihydrolipoyl transacetylase promotes chemotherapy resistance via mitochondrial tetrahydrofolate signaling.Nature communications · 2025Article
42 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolic enzymes and metabolites display non-metabolic functions in immune cell signalling that modulate immune attack ability. However, whether and how a tumour's metabolic remodelling contributes to its immune resistance remain to be clarified. Here we perform a functional screen of metabolic genes that rescue tumour cells from effector T cell cytotoxicity, and identify the embryo- and tumour-specific folate cycle enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2). Mechanistically, MTHFD2 promotes basal and IFN-γ-stimulated PD-L1 expression, which is necessary for tumourigenesis in vivo. Moreover, IFN-γ stimulates MTHFD2 through the AKT-mTORC1 pathway. Meanwhile, MTHFD2 drives the folate cycle to sustain sufficient uridine-related metabolites including UDP-GlcNAc, which promotes the global O-GlcNAcylation of proteins including cMYC, resulting in increased cMYC stability and PD-L1 transcription. Consistently, the O-GlcNAcylation level positively correlates with MTHFD2 and PD-L1 in pancreatic cancer patients. These findings uncover a non-metabolic role for MTHFD2 in cell signalling and cancer biology.
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