ArticleProceedings of the National Academy of Sciences of the United States of America2022
LPA suppresses T cell function by altering the cytoskeleton and disrupting immune synapse formation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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Who cites it
30 citing papers in PubMed, 37 citations in OpenAlex.
- Metabolic rewiring of the dendritic cell-T cell axis: tumour-derived barriers and therapeutic opportunities.Experimental & molecular medicine · 2026Review
- Metabolic modulation of immune cell function: mechanisms and therapeutic implications in cancer immunotherapy.Oncogenesis · 2026Review
- Organ-Specific Migration License (OSML) theory: a novel paradigm for spatiotemporal regulation and intervention of cross-organ immune cell migration in tumor immune responses.Cell communication and signaling : CCS · 2026Review
- Lysophosphatidylcholine 18:2 exacerbates Th17-dominant inflammation in obese asthma.Lipids in health and disease · 2026Article
- Targeting liver metastases in uveal melanoma: ATX-LPA mediated immunosuppression and novel therapeutic approaches.Frontiers in immunology · 2026Article
- Lpar5 regulates the CD8 T-cell response to persistent virus infection by altering exhaustion programming, survival, and NK receptor expression.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Decoding lysophosphatidic acid signaling in physiology and disease: mapping the multimodal and multinodal signaling networks.Signal transduction and targeted therapy · 2025Review
- Inhibition of autotaxin activity with IOA-289 decreases fibrosis in mouse E0771 breast tumors.International journal of cancer · 2025Article
- Phase 2 study design and analysis approach for BBT-877: an autotaxin inhibitor targeting idiopathic pulmonary fibrosis.BMJ open respiratory research · 2025Article
- Metal-modulated T cell antitumor immunity and emerging metalloimmunotherapy.Cancer metastasis reviews · 2025Review
- Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells.Journal of visualized experiments : JoVE · 2025Article
- Dysregulated ATX-LPA and YAP/TAZ signaling in dystrophic SgcdSkeletal muscle · 2025Article
- Cancer ATF4-mediated CD58 endocytosis impairs anti-tumor immunity and immunotherapy.Journal of translational medicine · 2025Article
- Biomechanics in the tumor microenvironment: from biological functions to potential clinical applications.Experimental hematology & oncology · 2025Review
- The CD38Frontiers in immunology · 2025Article
- Crosstalk between the tumor immune microenvironment and metabolic reprogramming in pancreatic cancer: new frontiers in immunotherapy.Frontiers in immunology · 2025Review
- AGPAT3 Regulates Immune Microenvironment in Osteosarcoma via Lysophosphatidic Acid Metabolism.Oncology research · 2025Article
- Gene Expression Dysregulation in Whole Blood of Patients withInternational journal of molecular sciences · 2024Article
- Deleting autotaxin in LysM+ myeloid cells impairs innate tumor immunity in models of metastatic melanoma.iScience · 2024Article
- GPCRs: emerging targets for novel T cell immune checkpoint therapy.Cancer immunology, immunotherapy : CII · 2024Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Cancer and chronic infections often increase levels of the bioactive lipid, lysophosphatidic acid (LPA), that we have demonstrated acts as an inhibitory ligand upon binding LPAR5 on CD8 T cells, suppressing cytotoxic activity and tumor control. This study, using human and mouse primary T lymphocytes, reveals how LPA disrupts antigen-specific CD8 T cell:target cell immune synapse (IS) formation and T cell function via competing for cytoskeletal regulation. Specifically, we find upon antigen-specific T cell:target cell formation, IP3R1 localizes to the IS by a process dependent on mDia1 and actin and microtubule polymerization. LPA not only inhibited IP3R1 from reaching the IS but also altered T cell receptor (TCR)–induced localization of RhoA and mDia1 impairing F-actin accumulation and altering the tubulin code. Consequently, LPA impeded calcium store release and IS-directed cytokine secretion. Thus, targeting LPA signaling in chronic inflammatory conditions may rescue T cell function and promote antiviral and antitumor immunity.
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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.