ArticleThe Journal of clinical investigation2023
Autotaxin suppresses cytotoxic T cells via LPAR5 to promote anti-PD-1 resistance in non-small cell lung cancer.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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.
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Who cites it
23 citing papers in PubMed, 23 citations in OpenAlex.
- Guiding the Application of Immunotherapy in Nonsmall Cell Lung Cancer: The Role of Biomarkers.Thoracic cancer · 2026Review
- Biology and function of the autotaxin/lysophosphatidic acid axis in cancer (Review).Molecular and clinical oncology · 2026Review
- GPNMB-directed CAR T cell therapy against MiT/TFE-family fusion-driven solid tumors.Nature cancer · 2026Article
- LPAR4 mediates resistance to interferon-induced stress in soft tissue sarcoma.Science advances · 2026Article
- Loss of miR-29a/b1 Cluster Reprograms the Tumor Microenvironment and Contributes to Immunosuppression in Lung Cancer.Cancer immunology research · 2026Article
- Risk stratification of PD-L1 expression in non-small cell lung cancer: a predictive model for prognosis.Journal of thoracic disease · 2026Article
- Identification and Functional Validation of PTH2R as a Therapeutic Target in Lung Adenocarcinoma.Biomedicines · 2026Article
- Metabolomics Reveals Potential Biomarkers for Early Detection of irAEs in ICI-Treated Patients.Drug design, development and therapy · 2026Article
- Decoding lysophosphatidic acid signaling in physiology and disease: mapping the multimodal and multinodal signaling networks.Signal transduction and targeted therapy · 2025Review
- How does lipid phosphatase 1 (LPP1) regulate antitumor CD8Immunity · 2025Article
- Synthesis of Autotaxin-Inhibiting Lipid Nanoparticles to Regulate Autophagy and Inflammatory Responses in Activated Macrophages.Tissue engineering and regenerative medicine · 2025Article
- Parabacteroides distasonis promotes CXCL9 secretion of tumor-associated macrophages and enhances CD8BMC biotechnology · 2025Article
- Pancreatic CAF-Derived Autotaxin Drives Autocrine CTGF Expression to Modulate Protumorigenic Signaling.Molecular cancer therapeutics · 2025Article
- LPA suppresses HLA-DR expression in human melanoma cells: a potential immune escape mechanism involving LPAR1 and DR6-mediated release of IL-10.Acta pharmacologica Sinica · 2025Article
- HPV-Associated Gene Signatures in Bladder Cancer: A Comprehensive Prognostic Model and its Implications in Immunotherapy.International journal of medical sciences · 2025Article
- AGPAT3 Regulates Immune Microenvironment in Osteosarcoma via Lysophosphatidic Acid Metabolism.Oncology research · 2025Article
- Fuel for thought: targeting metabolism in lung cancer.Translational lung cancer research · 2024Review
- Metabolic gatekeepers: harnessing tumor-derived metabolites to optimize T cell-based immunotherapy efficacy in the tumor microenvironment.Cell death & disease · 2024Review
- 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
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Non-small cell lung cancers that harbor concurrent KRAS and TP53 (KP) mutations are immunologically warm tumors with partial responsiveness to anti-PD-(L)1 blockade; however, most patients observe little or no durable clinical benefit. To identify novel tumor-driven resistance mechanisms, we developed a panel of KP murine lung cancer models with intrinsic resistance to anti-PD-1 and queried differential gene expression between these tumors and anti-PD-1-sensitive tumors. We found that the enzyme autotaxin (ATX), and the metabolite it produces, lysophosphatidic acid (LPA), were significantly upregulated in resistant tumors and that ATX directly modulated antitumor immunity, with its expression negatively correlating with total and effector tumor-infiltrating CD8+ T cells. Pharmacological inhibition of ATX, or the downstream receptor LPAR5, in combination with anti-PD-1 was sufficient to restore the antitumor immune response and efficaciously control lung tumor growth in multiple KP tumor models. Additionally, ATX was significantly correlated with inflammatory gene signatures, including a CD8+ cytolytic score in multiple lung adenocarcinoma patient data sets, suggesting that an activated tumor-immune microenvironment upregulates ATX and thus provides an opportunity for cotargeting to prevent acquired resistance to anti-PD-1 treatment. These data reveal the ATX/LPA axis as an immunosuppressive pathway that diminishes the immune checkpoint blockade response in lung 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 Socratic graph.