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.

中文翻译：

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中性粒细胞分析阐明了抗肿瘤抗原呈递效力

中性粒细胞是最丰富、最有效的病原体防御者，在各种癌症类型中发挥相反的功能。然而，鉴于中性粒细胞的半衰期较短，探索中性粒细胞如何在癌症中采取特定的命运仍然具有挑战性。在这里，我们生成并整合了 17 种癌症类型（来自 143 名患者的 225 个样本）的单细胞中性粒细胞转录组。中性粒细胞表现出非凡的复杂性，具有 10 种不同的状态，包括炎症、血管生成和抗原呈递。值得注意的是，抗原呈递程序与大多数癌症的良好生存相关，并且可以由亮氨酸代谢和随后的组蛋白 H3K27ac 修饰引起。这些中性粒细胞可以进一步激发（新）抗原特异性和抗原非依赖性 T 细胞反应。中性粒细胞输送或亮氨酸饮食可微调免疫平衡，从而增强各种小鼠癌症模型中的抗 PD-1 治疗。总之，这些数据不仅表明中性粒细胞在癌症之间的差异，而且还表明了治疗机会，例如抗原呈递中性粒细胞递送。