A single-cell analysis of the NK cell landscape reveals that dietary restriction boosts NK cell antitumor immunity via Eomesdermin

Natural killer (NK) cells are primarily responsible for tumor surveillance, and their activation entirely depends on optimal metabolic signals. The adaptation of NK cell anti-tumor responses to nutritional stress is still poorly understood. Here, based on single-cell RNA sequencing, we discovered that dietary restriction (DR) enriches the rejuvenated subset of CD27+CD11b+ NK cells and improves their activation via Eomesodermin (Eomes), a transcription factor upregulated during DR treatment. Eomes reverses the differentiation of rejuvenated to senescent NK cells by antagonizing the T-bet-Zeb2 axis while improving chemotaxis and adhesion. Furthermore, DR increases the chromatin accessibility of Eomes to genes that regulate chemotaxis and adhesion in NK cells. To summarize, tumor control under dietary restriction requires Eomes-regulated NK cell anti-tumor immunity. Overall design: NK cells were isolated from the spleen of normal and dietary restriction mice by flow cytometry, and analyzed using scRNAseq