ArticleCell metabolism2023
PHGDH-mediated endothelial metabolism drives glioblastoma resistance to chimeric antigen receptor T cell immunotherapy.
Article in Cell metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
87 citing papers in PubMed, 113 citations in OpenAlex.
- Stress-induced lipocalin 2 remodels the tumor microenvironment to exclude T cells.Molecular biomedicine · 2026Article
- Microenvironment-derived acetylated amino acids promote glioblastoma treatment resistance.Research square · 2026Article
- Blood-brain barrier and blood-tumoral barrier formation in glioblastoma: endothelial cells and glioblastoma stem cells at the immune-brain crossroad.Fluids and barriers of the CNS · 2026Review
- More than a ring: the emerging role of heme in angiogenesis.Cell communication and signaling : CCS · 2026Review
- Advances and challenges in glioblastoma immunotherapy: a meta-analysis of immune checkpoint inhibitors.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- PHGDH loss promotes hypoxia tolerance through glycolytic reprogramming and enhanced HIF-1 activity.Cell death discovery · 2026Article
- Molecular insights into DNA damage response plasticity in glioma stem cells.Communications biology · 2026Review
- ATF4 promotes immune evasion in oral squamous cell carcinoma by suppressing autophagic PD-L1 degradation.Journal for immunotherapy of cancer · 2026Article
- Gut Dysbiosis Serine-Glycine Metabolism and Glioblastoma: Exploring Therapeutic Opportunities.Cancers · 2026Review
- IGF2BP2-driven serine metabolism promotes the progression of thyroid carcinoma via mJournal of translational medicine · 2026Article
- The vascular niche: an orchestrator of the spatiotemporal dynamics of distant metastasis.Acta pharmacologica Sinica · 2026Review
- Article
- ATF4: Orchestrating Cellular Stress Adaptation, Metabolism, and Immune Regulation in Health and Disease.International journal of molecular sciences · 2026Review
- Targeting the noncanonical function of metabolic enzyme PHGDH in driving PD-L1 expression and cancer immune evasion.Cell reports. Medicine · 2026Article
- Review
- PSAT1 Promotes NSCLC Progression via the De Novo Serine Synthesis Pathway and Represents a Therapeutic Vulnerability.Cancer medicine · 2026Article
- Harnessing γδ T cells for B7-H3-targeting CAR therapy to enhance anti-tumor therapy in glioblastoma.Journal of translational medicine · 2026Article
- Taurochenodeoxycholic acid alleviates obesity-induced endothelial dysfunction.European heart journal · 2026Article
- Exploiting porphyrin metabolism to inhibit angiogenesis.Angiogenesis · 2026Article
- Microenvironmental regulation of solid tumour resistance to CAR T cell therapy.Nature reviews. Immunology · 2026Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 3 institutions in 1 country.
Funding
Abstract
The efficacy of immunotherapy is limited by the paucity of T cells delivered and infiltrated into the tumors through aberrant tumor vasculature. Here, we report that phosphoglycerate dehydrogenase (PHGDH)-mediated endothelial cell (EC) metabolism fuels the formation of a hypoxic and immune-hostile vascular microenvironment, driving glioblastoma (GBM) resistance to chimeric antigen receptor (CAR)-T cell immunotherapy. Our metabolome and transcriptome analyses of human and mouse GBM tumors identify that PHGDH expression and serine metabolism are preferentially altered in tumor ECs. Tumor microenvironmental cues induce ATF4-mediated PHGDH expression in ECs, triggering a redox-dependent mechanism that regulates endothelial glycolysis and leads to EC overgrowth. Genetic PHGDH ablation in ECs prunes over-sprouting vasculature, abrogates intratumoral hypoxia, and improves T cell infiltration into the tumors. PHGDH inhibition activates anti-tumor T cell immunity and sensitizes GBM to CAR T therapy. Thus, reprogramming endothelial metabolism by targeting PHGDH may offer a unique opportunity to improve T cell-based immunotherapy.
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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.