Topics

Pro-Survival Lipid Sphingosine-1-Phosphate Metabolically Programs T Cells to Limit Anti-tumor Activity.

08:00 EDT 13th August 2019 | BioPortfolio

Summary of "Pro-Survival Lipid Sphingosine-1-Phosphate Metabolically Programs T Cells to Limit Anti-tumor Activity."

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.

Affiliation

Journal Details

This article was published in the following journal.

Name: Cell reports
ISSN: 2211-1247
Pages: 1879-1893.e7

Links

DeepDyve research library

PubMed Articles [26841 Associated PubMed Articles listed on BioPortfolio]

Inhibition of the sphingosine-1-phosphate pathway promotes the resolution of neutrophilic inflammation.

Sphingosine-1-phosphate (S1P) is an important sphingolipid derived from plasma membrane and has a known role in productive phase of inflammation, but its role in neutrophil survival and resolution pha...

Topographical mapping of isoform-selectivity determinants for J-channel-binding inhibitors of sphingosine kinases 1 and 2.

Sphingosine kinase enzymes (SK1 and SK2) catalyse the conversion of sphingosine into sphingosine 1-phosphate and play a key role in lipid signaling and cellular responses. Mapping of isoform amino aci...

Upregulation of sphingosine-1-phosphate receptor 3 on fibroblast-like synoviocytes is associated with the development of collagen-induced arthritis via increased interleukin-6 production.

Sphingosine-1-phosphate receptor 3 (S1P3) is one of five receptors for sphingosine-1-phosphate (S1P). S1P/S1P3 signaling is involved in numerous physiological and pathological processes including bone...

Ceramide and sphingosine 1-phosphate in adipose dysfunction.

The increased adipose tissue mass of obese individuals enhances the risk of metabolic syndrome, type 2 diabetes and cardiovascular diseases. During pathological expansion of adipose tissue, multiple m...

Ceramide and sphingosine 1-phosphate in adipose dysfunction.

The increased adipose tissue mass of obese individuals enhances the risk of metabolic syndrome, type 2 diabetes and cardiovascular diseases. During pathological expansion of adipose tissue, multiple m...

Clinical Trials [13962 Associated Clinical Trials listed on BioPortfolio]

Anti-Inflammatory Pulmonal Therapy of CF-Patients With Amitriptyline and Placebo

Our data indicate that the CFTR-molecule functions as a transporter for sphingosine-1-phosphate and sphingosine or regulates the uptake of these sphingolipids by epithelial cells. The dist...

Evaluation of Plasma Sphingosine-1-Phosphate as A Diagnostic and Prognostic Biomarkers of Community-Acquired Pneumonia

Pneumonia is a major infectious cause of death worldwide and imposes a considerable burden on healthcare resources. Obstructive lung diseases (COPD and Asthma) are increasingly important c...

Sphingosine-1-phosphate and Pneumonia

Pneumonia is a major infectious cause of death worldwide and imposes a considerable burden on healthcare resources. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid and involved i...

Safety Study of iSONEP (Sonepcizumab/LT1009) to Treat Neovascular Age-related Macular Degeneration

Age-related macular degeneration (AMD) is a disease that, in time, destroys the macula, which is the central part of the retina that gives sharp central vision. The primary purpose of this...

Monitoring Natural Killer Cells in Multiple Sclerosis Patients Treated With Fingolimod

Data on fingolimod effects on NK cells are so far conflicting. A longitudinal study on fingolimod treated kidney transplant patients showed that NK cells were not influenced in any of the ...

Medical and Biotech [MESH] Definitions

A subfamily of lysophospholipid receptors with specificity for LYSOSPHINGOLIPIDS such as sphingosine-1-phosphate and sphingosine phosphorylcholine.

A sphingosine-derivative and IMMUNOSUPPRESSIVE AGENT that blocks the migration and homing of LYMPHOCYTES to the CENTRAL NERVOUS SYSTEM through its action on SPHINGOSINE 1-PHOSPHATE RECEPTORS. It is used in the treatment of MULTIPLE SCLEROSIS.

An amino alcohol with a long unsaturated hydrocarbon chain. Sphingosine and its derivative sphinganine are the major bases of the sphingolipids in mammals. (Dorland, 28th ed)

A perilipin that localizes to LIPID DROPLETS; CYTOPLASM; ENDOSOMES; and PLASMA MEMBRANE, especially in MACROPHAGES. It functions as a transporter of free fatty acids to lipid droplets to promote their biogenesis and growth. It is also required for the transport of the MANNOSE-6-PHOSPHATE RECEPTOR from endosomes to the TRANS-GOLGI NETWORK. Its structure consists of four helix bundles that interact with the hydrophobic lipid droplet surface.

A family of vertebrate and insect lipid droplet associated proteins. They consist of a conserved N-terminal PAT domain (an alpha-helical region of about 110 amino acids), an 11-mer repeat region, and lipid-binding hydrophobic regions or 4-helix bundles near their C-termini. Perilipins transiently or constitutively localize to LIPID DROPLETS in ADIPOCYTES and FOAM CELLS, especially in regions adjacent to the PLASMA MEMBRANE and ENDOPLASMIC RECTICULUM. They are critical for lipid droplet synthesis and homeostasis as well as the regulation of lipid metabolism. Genetic variations in perilipins are associated with ATHEROSCLEROSIS; OBESITY; and DIABETES MELLITUS.

Quick Search


DeepDyve research library

Relevant Topics

Cancer
  Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...

Melanoma
Melanoma is a highly malignant tumor of melanin-forming cells (melanocytes) There are most commonly found in the skin (resulting from sunlight exposure), but also in the eyes and mucous membranes. Metastasis to other regions of the body is also common....


Searches Linking to this Article