ArticleCancer discovery2022
Tumor-Derived Lysophosphatidic Acid Blunts Protective Type I Interferon Responses in Ovarian Cancer.
Article in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 56 citations in OpenAlex.
- LPA₃ signaling and biological functions: from physiological regulation to disease-targeted therapy.Molecular biology reports · 2026Review
- Robust Scoring System to Evaluate Animal Well-Being in Murine (Mus musculus) Orthotopic Breast Cancer and Ovarian Cancer Models.Journal of the American Association for Laboratory Animal Science : JAALAS · 2026Article
- Targeting DGAT1 reprograms lipid landscape and restores CD8⁺ T cell immunity in pancreatic cancer.Nature communications · 2026Article
- Rethinking ovarian cancer III: the past decade and future directions.Nature reviews. Cancer · 2026Review
- Inhibition of salt-inducible kinases reprograms T cells and antitumor immunity in ovarian cancer.Nature immunology · 2026Article
- Betrixaban activates cGAS-STING to promote antitumor immunity without pathological inflammation.EMBO molecular medicine · 2026Article
- Ex Vivo Immuno-Oncology Platform Reveals Spatial T-cell Infiltration Patterns Linked to ATR Inhibition Responses in High-Grade Serous Ovarian Cancer.Cancer immunology research · 2026Article
- Inflammatory milieu and role of epigenetic modifications in high-grade serous ovarian cancer.Clinical epigenetics · 2026Review
- Lipid remodeling and ferroptosis in phosphatidylcholine-mediated tumor-stroma crosstalk.Frontiers in molecular biosciences · 2026Review
- Inhibition of autotaxin sensitizes colon cancer to radiation by suppressing LPAR2-AKT survival signaling.BMC gastroenterology · 2025Article
- Dietary Polyunsaturated Fatty Acids Regulate Dendritic Cell Function via Nrf2-dependent Control of Ferroptosis.Research square · 2025Article
- How does lipid phosphatase 1 (LPP1) regulate antitumor CD8Immunity · 2025Article
- High Co-Expression ofBiomedicines · 2025Article
- Acid phosphatase type 6 promotes endometrial cancer progression via activating PI3K/AKT pathway.Molecular biology reports · 2025Article
- A noncanonical role of SAT1 enables anchorage independence and peritoneal metastasis in ovarian cancer.Nature communications · 2025Article
- Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells.Journal of visualized experiments : JoVE · 2025Article
- Crosstalk between stromal, immune, and ovarian cancer cells in lipid-rich tumor microenvironment exhibits proliferative features.Frontiers in immunology · 2025Review
- Tertiary lymphoid structures: exploring opportunities to improve immunotherapy in ovarian cancer.Frontiers in immunology · 2025Review
- Polymer Nanoparticles Advancements for Gynecological Cancers.International journal of nanomedicine · 2025Review
- Spatial profiling of the metabolism-immune axis in ovarian cancer.Frontiers in pharmacology · 2025Review
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21 authors at 10 institutions in 3 countries.
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Abstract
Lysophosphatidic acid (LPA) is a bioactive lipid enriched in the tumor microenvironment of immunosuppressive malignancies such as ovarian cancer. Although LPA enhances the tumorigenic attributes of cancer cells, the immunomodulatory activity of this phospholipid messenger remains largely unexplored. Here, we report that LPA operates as a negative regulator of type I interferon (IFN) responses in ovarian cancer. Ablation of the LPA-generating enzyme autotaxin (ATX) in ovarian cancer cells reprogrammed the tumor immune microenvironment, extended host survival, and improved the effects of therapies that elicit protective responses driven by type I IFN. Mechanistically, LPA sensing by dendritic cells triggered PGE2 biosynthesis that suppressed type I IFN signaling via autocrine EP4 engagement. Moreover, we identified an LPA-controlled, immune-derived gene signature associated with poor responses to combined PARP inhibition and PD-1 blockade in patients with ovarian cancer. Controlling LPA production or sensing in tumors may therefore be useful to improve cancer immunotherapies that rely on robust induction of type I IFN. SIGNIFICANCE: This study uncovers that ATX-LPA is a central immunosuppressive pathway in the ovarian tumor microenvironment. Ablating this axis sensitizes ovarian cancer hosts to various immunotherapies by unleashing protective type I IFN responses. Understanding the immunoregulatory programs induced by LPA could lead to new biomarkers predicting resistance to immunotherapy in patients with cancer. See related commentary by Conejo-Garcia and Curiel, p. 1841. This article is highlighted in the In This Issue feature, p. 1825.
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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.