Inducing trained immunity in pro-metastatic macrophages to control tumor metastasis.

Autor: Ding C; Division of Immunotherapy, The Hiram C. Polk, Jr., MD Department of Surgery, Immuno-Oncology Program, Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA., Shrestha R; Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, USA., Zhu X; Division of Immunotherapy, The Hiram C. Polk, Jr., MD Department of Surgery, Immuno-Oncology Program, Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA., Geller AE; Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, USA., Wu S; Division of Immunotherapy, The Hiram C. Polk, Jr., MD Department of Surgery, Immuno-Oncology Program, Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA., Woeste MR; Division of Immunotherapy, The Hiram C. Polk, Jr., MD Department of Surgery, Immuno-Oncology Program, Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA.; Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, USA., Li W; Department of Chemistry, Indiana University, Bloomington, IN, USA., Wang H; Department of Chemistry, Lehigh University, Bethlehem, PA, USA., Yuan F; Department of Chemistry, University of Louisville, Louisville, KY, USA., Xu R; Department of Chemistry, University of Louisville, Louisville, KY, USA., Chariker JH; Department of Neuroscience, KBRIN Bioinformatics Core, University of Louisville, Louisville, KY, USA., Hu X; Division of Immunotherapy, The Hiram C. Polk, Jr., MD Department of Surgery, Immuno-Oncology Program, Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA., Li H; Functional Immunomics Core, Brown Cancer Center, University of Louisville, Louisville, KY, USA., Tieri D; Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY, USA., Zhang HG; Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, USA., Rouchka EC; Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY, USA.; Department of Computer Science and Engineering, University of Louisville, Louisville, KY, USA., Mitchell R; Division of Immunotherapy, The Hiram C. Polk, Jr., MD Department of Surgery, Immuno-Oncology Program, Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA., Siskind LJ; Department of Pharmacology & Toxicology, University of Louisville School of Medicine, Louisville, KY, USA., Zhang X; Department of Chemistry, University of Louisville, Louisville, KY, USA., Xu XG; Department of Chemistry, Lehigh University, Bethlehem, PA, USA., McMasters KM; Division of Immunotherapy, The Hiram C. Polk, Jr., MD Department of Surgery, Immuno-Oncology Program, Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA., Yu Y; Department of Chemistry, Indiana University, Bloomington, IN, USA., Yan J; Division of Immunotherapy, The Hiram C. Polk, Jr., MD Department of Surgery, Immuno-Oncology Program, Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA. jun.yan@louisville.edu.; Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, USA. jun.yan@louisville.edu.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2023 Feb; Vol. 24 (2), pp. 239-254. Date of Electronic Publication: 2023 Jan 05.
DOI: 10.1038/s41590-022-01388-8
Abstrakt: Metastasis is the leading cause of cancer-related deaths and myeloid cells are critical in the metastatic microenvironment. Here, we explore the implications of reprogramming pre-metastatic niche myeloid cells by inducing trained immunity with whole beta-glucan particle (WGP). WGP-trained macrophages had increased responsiveness not only to lipopolysaccharide but also to tumor-derived factors. WGP in vivo treatment led to a trained immunity phenotype in lung interstitial macrophages, resulting in inhibition of tumor metastasis and survival prolongation in multiple mouse models of metastasis. WGP-induced trained immunity is mediated by the metabolite sphingosine-1-phosphate. Adoptive transfer of WGP-trained bone marrow-derived macrophages reduced tumor lung metastasis. Blockade of sphingosine-1-phosphate synthesis and mitochondrial fission abrogated WGP-induced trained immunity and its inhibition of lung metastases. WGP also induced trained immunity in human monocytes, resulting in antitumor activity. Our study identifies the metabolic sphingolipid-mitochondrial fission pathway for WGP-induced trained immunity and control over metastasis.
(© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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