Fasting reshapes tissue-specific niches to improve NK cell-mediated anti-tumor immunity.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Cell Press Country of Publication: United States NLM ID: 9432918 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4180 (Electronic) Linking ISSN: 10747613 NLM ISO Abbreviation: Immunity Subsets: MEDLINE
    • Publication Information:
      Publication: Cambridge, MA : Cell Press
      Original Publication: Cambridge, Mass. : Cell Press, c1994-
    • Subject Terms:
      Killer Cells, Natural*/immunology ; Killer Cells, Natural*/metabolism ; Fasting* ; Mice, Inbred C57BL*; Animals ; Mice ; Humans ; Neoplasms/immunology ; Bone Marrow/immunology ; Bone Marrow/metabolism ; Mice, Knockout ; Interferon-gamma/metabolism ; Interferon-gamma/immunology ; Spleen/immunology ; Spleen/metabolism ; Immunity, Innate/immunology ; Interleukin-12/metabolism ; Interleukin-12/immunology ; Receptors, CXCR4/metabolism
    • Abstract:
      Fasting is associated with improved outcomes in cancer. Here, we investigated the impact of fasting on natural killer (NK) cell anti-tumor immunity. Cyclic fasting improved immunity against solid and metastatic tumors in an NK cell-dependent manner. During fasting, NK cells underwent redistribution from peripheral tissues to the bone marrow (BM). In humans, fasting also reduced circulating NK cell numbers. NK cells in the spleen of fasted mice were metabolically rewired by elevated concentrations of fatty acids and glucocorticoids, augmenting fatty acid metabolism via increased expression of the enzyme CPT1A, and Cpt1a deletion impaired NK cell survival and function in this setting. In parallel, redistribution of NK cells to the BM during fasting required the trafficking mediators S1PR5 and CXCR4. These cells were primed by an increased pool of interleukin (IL)-12-expressing BM myeloid cells, which improved IFN-γ production. Our findings identify a link between dietary restriction and optimized innate immune responses, with the potential to enhance immunotherapy strategies.
      Competing Interests: Declaration of interests The authors declare no competing interests.
      (Copyright © 2024 Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: NK cells; anti-tumor responses; fasting; immunometabolism; innate immunity; metabolism
    • Accession Number:
      82115-62-6 (Interferon-gamma)
      187348-17-0 (Interleukin-12)
      0 (Receptors, CXCR4)
    • Publication Date:
      Date Created: 20240615 Date Completed: 20240814 Latest Revision: 20240815
    • Publication Date:
      20240816
    • Accession Number:
      10.1016/j.immuni.2024.05.021
    • Accession Number:
      38878769