High-salt diet mediates interplay between NK cells and gut microbiota to induce potent tumor immunity.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34516769.
- Also identified by DOI 10.1126/sciadv.abg5016 and PMC identifier 8442882.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
High-salt diet (HSD) modulates effector and regulatory T cell functions and promotes tissue inflammation in autoimmune diseases. However, effects of HSD and its association with gut microbiota in tumor immunity remain undefined. Here, we report that HSD induces natural killer (NK) cell–mediated tumor immunity by inhibiting PD-1 expression while enhancing IFNγ and serum hippurate. Salt enhanced tumor immunity when combined with a suboptimal dose of anti-PD1 antibody. While HSD-induced tumor immunity was blunted upon gut microbiota depletion, fecal microbiota transplantation (FMT) from HSD mice restored the tumor immunity associated with NK cell functions. HSD increased the abundance of <i>Bifidobacterium</i> and caused increased gut permeability leading to intratumor localization of <i>Bifidobacterium</i>, which enhanced NK cell functions and tumor regression. Intratumoral injections of <i>Bifidobacterium</i> activated NK cells, which inhibited tumor growth. These results indicate that HSD modulates gut microbiome that induces NK cell–dependent tumor immunity with a potential translational perspective.