ArticleCell reports2019
Pro-Survival Lipid Sphingosine-1-Phosphate Metabolically Programs T Cells to Limit Anti-tumor Activity.
Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
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- Tumor and Stromal Sphingolipid Imbalance Are Associated with T Cell Tissue Residency in Glioblastoma.Cancers · 2026Article
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- SPHK1 deficiency promotes intestinal homeostasis by ameliorating ER stress-induced gastrointestinal injury during murine graft-versus-host disease.Science China. Life sciences · 2026Article
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- Identification of ion homeostasis-related genes as diagnostic biomarkers for pulmonary arterial hypertension via WGCNA and machine learning.Frontiers in genetics · 2026Article
- Ceramidase is involved in metabolic reprogramming of fibroblasts under hypoxia conditions.Frontiers in physiology · 2026Article
- Pyruvate kinase M2 -mediated histone lactylation alters three-dimensional genomic architecture in polycystic ovary syndrome.Signal transduction and targeted therapy · 2025Article
- Gut microbiota shapes cancer immunotherapy responses.NPJ biofilms and microbiomes · 2025Review
- A Review Discussing Synthesis and Translational Studies of Medicinal Agents Targeting Sphingolipid Pathways.Biomolecules · 2025Review
- Selective requirement of glycosphingolipid synthesis for natural killer and cytotoxic T cells.Cell · 2025Article
- Acid ceramidase controls proteasome inhibitor resistance and is a novel therapeutic target for the treatment of relapsed/refractory multiple myeloma.Haematologica · 2025Article
- ATP11B triggers the infiltration of T cells into GBM and intensifies anti-GBM immunity by upregulating and externalizing S1PR1.Journal of translational medicine · 2025Article
- Sphingolipid synthesis in tumor-associated macrophages confers immunotherapy resistance in hepatocellular carcinoma.Science advances · 2025Article
- Sphingosine-1-Phosphate Metabolic Pathway in Cancer: Implications for Therapeutic Targets.International journal of molecular sciences · 2025Review
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- Synergistic effect of the sphingosine kinase inhibitor safingol in combination with 2'-nitroflavone in breast cancer.Journal of molecular medicine (Berlin, Germany) · 2024Article
14 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
23 authors at 3 institutions in 1 country.
Funding
Abstract
Sphingosine 1-phosphate (S1P), a bioactive lysophospholipid generated by sphingosine kinase 1 (SphK1), regulates lymphocyte egress into circulation via S1P receptor 1 (S1PR1) signaling, and it controls the differentiation of regulatory T cells (Tregs) and T helper-17 cells. However, the mechanisms by which receptor-independent SphK1-mediated intracellular S1P levels modulate T cell functionality remains unknown. We show here that SphK1-deficient T cells maintain central memory phenotype and exhibit higher mitochondrial respiration and reduced differentiation to Tregs. Mechanistically, we discovered a direct correlation between SphK1-generated S1P and lipid transcription factor PPARγ (peroxisome proliferator-activated receptor gamma) activity, which in turn regulates lipolysis in T cells. Genetic and pharmacologic inhibition of SphK1 improved metabolic fitness and anti-tumor activity of T cells against murine melanoma. Further, inhibition of SphK1 and PD1 together led to improved control of melanoma. Overall, these data highlight the clinical potential of limiting SphK1/S1P signaling for enhancing anti-tumor-adoptive T cell therapy.
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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.