AI Article Synopsis

  • Autotaxin (ATX) is an enzyme that produces lysophosphatidic acid (LPA), which influences cancer spread, treatment resistance, and immune responses in tumors.
  • Researchers discovered that myeloid cells in melanoma biopsies highly express ATX and studied its effect on tumor immunity in two melanoma models (spontaneous and experimental).
  • Knockout of ATX in specific myeloid cells reduced melanoma metastasis by over 50%, revealing important immune differences in the tumor environment that change depending on the type of model used.

Article Abstract

Autotaxin (ATX) is a lysophospholipase D that generates lysophosphatidic acid (LPA) and regulates cancer metastasis, therapeutic resistance, and tumor immunity. We found that myeloid cells in human melanoma biopsies abundantly express ATX and investigated its role in modulating innate tumor immunity using two models of melanoma metastasis-spontaneous and experimental. Targeted knockout of ATX in LysM+ myeloid cells in mice (LysM-KO) reduced both spontaneous and experimental B16-F10 melanoma metastases by ≥ 50%. Immunoprofiling revealed differences in M2-like alveolar macrophages, neutrophils and regulatory T cells in the metastatic lungs of LysM-WT versus LysM-KO that are model-dependent. These differences extend systemically, with LysM-KO mice bearing experimental metastasis having fewer neutrophils in the spleen than LysM-WT mice. Our results show that (1) LysM+ myeloid cells are an important source of ATX/LPA that promote melanoma metastasis by altering innate tumor immunity, and (2) intratumor and systemic immune profiles vary dynamically during disease progression and are model-dependent.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467674PMC
http://dx.doi.org/10.1016/j.isci.2024.110971DOI Listing

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