Fasting reshapes tissue-specific niches to improve NK cell-mediated anti-tumor immunity Journal Article
| Authors: | Delconte, R. B.; Owyong, M.; Santosa, E. K.; Srpan, K.; Sheppard, S.; McGuire, T. J.; Abbasi, A.; Diaz-Salazar, C.; Chun, J.; Rogatsky, I.; Hsu, K. C.; Jordan, S.; Merad, M.; Sun, J. C. |
| Article Title: | Fasting reshapes tissue-specific niches to improve NK cell-mediated anti-tumor immunity |
| 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. © 2024 Elsevier Inc. |
| Keywords: | adult; controlled study; protein expression; human cell; gene deletion; nonhuman; neoplasm; neoplasms; animal cell; mouse; animal; metabolism; animals; mice; mice, knockout; animal tissue; cell survival; cell function; bone marrow; spleen; animal experiment; animal model; mice, inbred c57bl; c57bl mouse; immunology; gamma interferon; natural killer cell; killer cells, natural; tumor immunity; innate immunity; immunity, innate; bone marrow cell; interferon-gamma; fatty acid; diet restriction; fasting; interleukin 12; knockout mouse; tissue specificity; receptors, cxcr4; tumor microenvironment; chemokine receptor cxcr4; interleukin-12; nk cells; fatty acid metabolism; interferon production; corticosterone; metabolic reprogramming; humans; human; male; female; article; immunometabolism; anti-tumor responses |
| Journal Title: | Immunity |
| Volume: | 57 |
| Issue: | 8 |
| ISSN: | 1074-7613 |
| Publisher: | Cell Press |
| Date Published: | 2024-08-13 |
| Start Page: | 1923 |
| End Page: | 1938.e7 |
| Language: | English |
| DOI: | 10.1016/j.immuni.2024.05.021 |
| PUBMED: | 38878769 |
| PROVIDER: | scopus |
| PMCID: | PMC11684419 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK authors: Rebecca B. Delconte and Joseph C. Sun -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work