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

First Author  Delconte RB Year  2024
Journal  Immunity Volume  57
Issue  8 Pages  1923-1938.e7
PubMed ID  38878769 Mgi Jnum  J:352543
Mgi Id  MGI:7665167 Doi  10.1016/j.immuni.2024.05.021
Citation  Delconte RB, et al. (2024) Fasting reshapes tissue-specific niches to improve NK cell-mediated anti-tumor immunity. Immunity
abstractText  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-gamma production. Our findings identify a link between dietary restriction and optimized innate immune responses, with the potential to enhance immunotherapy strategies.
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