{Reference Type}: Journal Article
{Title}: Neutrophil profiling illuminates anti-tumor antigen-presenting potency.
{Author}: Wu Y;Ma J;Yang X;Nan F;Zhang T;Ji S;Rao D;Feng H;Gao K;Gu X;Jiang S;Song G;Pan J;Zhang M;Xu Y;Zhang S;Fan Y;Wang X;Zhou J;Yang L;Fan J;Zhang X;Gao Q;
{Journal}: Cell
{Volume}: 187
{Issue}: 6
{Year}: 2024 Mar 14
{Factor}: 66.85
{DOI}: 10.1016/j.cell.2024.02.005
{Abstract}: Neutrophils, the most abundant and efficient defenders against pathogens, exert opposing functions across cancer types. However, given their short half-life, it remains challenging to explore how neutrophils adopt specific fates in cancer. Here, we generated and integrated single-cell neutrophil transcriptomes from 17 cancer types (225 samples from 143 patients). Neutrophils exhibited extraordinary complexity, with 10 distinct states including inflammation, angiogenesis, and antigen presentation. Notably, the antigen-presenting program was associated with favorable survival in most cancers and could be evoked by leucine metabolism and subsequent histone H3K27ac modification. These neutrophils could further invoke both (neo)antigen-specific and antigen-independent T cell responses. Neutrophil delivery or a leucine diet fine-tuned the immune balance to enhance anti-PD-1 therapy in various murine cancer models. In summary, these data not only indicate the neutrophil divergence across cancers but also suggest therapeutic opportunities such as antigen-presenting neutrophil delivery.