ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2022
Tumor Derived Extracellular Vesicles Drive T Cell Exhaustion in Tumor Microenvironment through Sphingosine Mediated Signaling and Impacting Immunotherapy Outcomes in Ovarian Cancer.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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.
The trial behind it
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Who cites it
45 citing papers in PubMed, 69 citations in OpenAlex.
- Lipid Cargo of Small Extracellular Vesicles as a Novel Contributor to Cardiovascular Diseases.International journal of molecular sciences · 2026Review
- MEOX1 Coordinates Autocrine-Paracrine Programs via SPHK1/S1P to Promote Lymph Node Metastasis in Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Extracellular vesicles derived from ovarian cancer cells promote tumor progression through m2 macrophage polarization and enhanced angiogenesis.BMC cancer · 2026Article
- Diagnostic Potential of Exosomes in Colorectal Cancer: Current Advances and Future Perspectives.Molecules (Basel, Switzerland) · 2026Review
- Review
- The emerging role of SPHK1 at the immune-metabolic interface: a pan-cancer integrative analysis.Scientific reports · 2026Article
- Aberrant lipid metabolism reshapes the immune landscape in bone metastasis of nasopharyngeal carcinoma.Journal for immunotherapy of cancer · 2025Article
- Conserved sphingolipid metabolism under transcriptomic diversity: a prognostic and therapeutic target in triple-negative breast cancer.Journal of translational medicine · 2025Article
- eIF4E Enriched Extracellular Vesicles Induce Immunosuppressive Macrophages through HMGCR-Mediated Metabolic Rewiring.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Combination of PF-543 and TRAIL Effectively Induces Apoptotic Cell Death and Inhibits Stem Cell-Like Properties Through the SPHK1/S1PR1/STAT3 Pathway in TRAIL-Resistant Colorectal Cancer Cells.Digestive diseases and sciences · 2025Article
- Advances and obstacles of T cell-based immunotherapy in gynecological malignancies.Molecular cancer · 2025Review
- Immunosuppressive Effects of Multiple Myeloma-Derived Extracellular Vesicles Through T Cell Exhaustion.Cancer science · 2025Article
- Extracellular Vesicle Lipids and Their Role in Delivery.Journal of extracellular biology · 2025Review
- Extracellular vesicles isolated from SphK1 inhibitor SKI II-medium restrain the migration of colorectal cancer.Translational cancer research · 2025Article
- Identification of Sphingosine Kinase 1 as a Novel Protein Regulated by High Molecular Weight Hyaluronan in Ovarian Cancer.Journal of cellular and molecular medicine · 2025Article
- Exosomal SphK1 from colorectal cancer cells promotes cancer cell migration and activates hepatic stellate cells.Molecular medicine reports · 2025Article
- Exosomal Lipids in Cancer Progression and Metastasis.Cancer medicine · 2025Review
- Natural and Bioengineered Extracellular Vesicles in Diagnosis, Monitoring and Treatment of Cancer.ACS nano · 2025Review
- SPHK1 enhances olaparib resistance in ovarian cancer through the NFκB/NRF2/ferroptosis pathway.Cell death discovery · 2025Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
Abstract
SPHK1 (sphingosine kinase-1) catalyzes the phosphorylation of sphingosine to sphingosine-1-phosphate (S1P), is found to be highly expressed in solid tumors. Here, extracellular vesicles (EVs) are identified as the key transporters of SPHK1 to the tumor microenvironment. Consequently, SPHK1-packaged EVs elevate S1P levels in the tumor microenvironment, where S1P appears as an immunosuppressive agent. However, the exact mechanism of how S1P mediates its immunosuppressive effects in cancer is not understood. It is investigated that S1P can induce T cell exhaustion. S1P can also upregulate programmed death ligand-1 (PDL-1) expression through E2F1-mediated transcription. Notably, an SPHK1 inhibitor PF543 improves T cell-mediated cytotoxicity. Furthermore, combining PF543 with an anti-PD-1 antibody reduces tumor burden and metastasis more effectively than PF543 alone in vivo. These data demonstrate a previously unrecognized mechanism of how SPHK1-packaged EVs contribute to the progression of ovarian cancer and thus present the potential clinical application of inhibiting SPHK1/S1P signaling to improve immune checkpoint blockage (anti-PD-1 antibody) therapy in ovarian cancer.
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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.