ArticleCellular & molecular immunology2024
Targeting PHGDH reverses the immunosuppressive phenotype of tumor-associated macrophages through α-ketoglutarate and mTORC1 signaling.
Article in Cellular & molecular immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 62 citations in OpenAlex.
- Targeting myeloid cell plasticity and metabolic reprogramming to alleviate T cell dysfunction and exhaustion-associated states and enhance immune checkpoint blockade therapy.Biomarker research · 2026Review
- An Avalanche Effect Nanomodulator Triggers Cascade Ferroptosis/Cuproptosis for Immunosuppressive Microenvironment Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting the cancer metabolism-immunity interface: update and perspectives.Experimental hematology & oncology · 2026Review
- The competition of amino acid among tumors, tumor-associated macrophages and T cells based on metabolic reprogramming.iScience · 2026Review
- Dynamic remodeling of amino acid metabolism in tumor-associated macrophages: Fueling immunosuppression, reshaping tumor niches, and unlocking metabolic checkpoints.Journal of advanced research · 2026Review
- Amino Acids as Targets for Immunotherapy against Solid Tumors.Cell biochemistry and biophysics · 2026Review
- IGF2BP2-driven serine metabolism promotes the progression of thyroid carcinoma via mJournal of translational medicine · 2026Article
- Construction of a novel signature based on CRISPR-Cas9 screening for prognostic prediction in breast cancer.BMC cancer · 2026Article
- Glucose metabolic reprogramming as a driver of immunosuppression in the tumour microenvironment.Clinical and translational medicine · 2026Review
- L-serine at the crossroads of microbiota, intestinal health, and disorders.Communications biology · 2026Review
- Targeting the noncanonical function of metabolic enzyme PHGDH in driving PD-L1 expression and cancer immune evasion.Cell reports. Medicine · 2026Article
- PHGDH Orchestrates Cell Cycle Progression to Drive Cardiomyocyte Proliferation and Myocardial Regeneration via TGF-β/Smad Signalling Pathway.Cell proliferation · 2026Article
- Review
- Exercise Reprograms the Spatial Function of Phosphoglycerate Dehydrogenase of a Pathogenic Nuclear Transcription Factor (PHGDH): A Narrative Review.Metabolites · 2026Review
- Molecular and cellular landscapes of the immune microenvironment and multiomic biomarker-sets in platinum-resistant recurrent ovarian cancers.Journal of ovarian research · 2026Review
- Kernel-DMD for multiome data integration and control.PLoS computational biology · 2026Article
- Targeting metabolic-epigenetic-immune axis in cancer: molecular mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Cancer cachexia: molecular basis and therapeutic advances.Signal transduction and targeted therapy · 2026Review
- TREM2-Mediated Cholesterol Efflux in Macrophages Inhibits Anti-Tumor Immunity via Limitation of CD4Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Metabolic symbiosis and competition: the dual nature of TAM-tumor cell cross-talk in tumor progression.Frontiers in oncology · 2026Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Phosphoglycerate dehydrogenase (PHGDH) has emerged as a crucial factor in macromolecule synthesis, neutralizing oxidative stress, and regulating methylation reactions in cancer cells, lymphocytes, and endothelial cells. However, the role of PHGDH in tumor-associated macrophages (TAMs) is poorly understood. Here, we found that the T helper 2 (Th2) cytokine interleukin-4 and tumor-conditioned media upregulate the expression of PHGDH in macrophages and promote immunosuppressive M2 macrophage activation and proliferation. Loss of PHGDH disrupts cellular metabolism and mitochondrial respiration, which are essential for immunosuppressive macrophages. Mechanistically, PHGDH-mediated serine biosynthesis promotes α-ketoglutarate production, which activates mTORC1 signaling and contributes to the maintenance of an M2-like macrophage phenotype in the tumor microenvironment. Genetic ablation of PHGDH in macrophages from tumor-bearing mice results in attenuated tumor growth, reduced TAM infiltration, a phenotypic shift of M2-like TAMs toward an M1-like phenotype, downregulated PD-L1 expression and enhanced antitumor T-cell immunity. Our study provides a strong basis for further exploration of PHGDH as a potential target to counteract TAM-mediated immunosuppression and hinder tumor progression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.