复旦大学附属中山医院樊嘉院士和高强教授、中国科学院上海免疫与感染研究所张晓明研究员、复旦大学生物医学研究院杨力研究员，合作报道了中性粒细胞谱分析阐明了抗肿瘤抗原呈递效能。该研究于2024年3月5日发表于国际一流学术期刊《细胞》杂志上。
该团队从17种癌症类型(来自143名患者的225个样本)中生成并整合了单细胞中性粒细胞转录组数据。中性粒细胞表现出非凡的复杂性，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中的良好生存相关，并且可以通过亮氨酸代谢和随后的组蛋白H3K27乙酰化修饰来激活。
这些中性粒细胞还可以激发（新）抗原特异性和非特异性T细胞应答。在各种小鼠癌症模型中，中性粒细胞输送或亮氨酸饮食微调了免疫平衡，增强了抗PD-1疗法的效果。总之，这些数据不仅表明了中性粒细胞在癌症中的差异，还提出了诸如抗原呈递中性粒细胞递送等治疗可能。
研究人员表示，中性粒细胞是对抗病原体的最丰富和最有效的防御者，在各种类型的癌症中发挥对抗作用。然而，鉴于它们的半衰期很短，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。
附：英文原文
Title: Neutrophil profiling illuminates anti-tumor antigen-presenting potency
Author: Yingcheng Wu, Jiaqiang Ma, Xupeng Yang, Fang Nan, Tiancheng Zhang, Shuyi Ji, Dongning Rao, Hua Feng, Ke Gao, Xixi Gu, Shan Jiang, Guohe Song, Jiaomeng Pan, Mao Zhang, Yanan Xu, Shu Zhang, Yihui Fan, Xiaoying Wang, Jian Zhou, Li Yang, Jia Fan, Xiaoming Zhang, Qiang Gao
Issue&Volume: 2024-03-05
Abstract: Neutrophils, the most abundant and efficient defenders against pathogens, exert opposingfunctions across cancer types. However, given their short half-life, it remains challengingto explore how neutrophils adopt specific fates in cancer. Here, we generated andintegrated single-cell neutrophil transcriptomes from 17 cancer types (225 samplesfrom 143 patients). Neutrophils exhibited extraordinary complexity, with 10 distinctstates including inflammation, angiogenesis, and antigen presentation. Notably, theantigen-presenting program was associated with favorable survival in most cancersand could be evoked by leucine metabolism and subsequent histone H3K27ac modification.These neutrophils could further invoke both (neo)antigen-specific and antigen-independentT cell responses. Neutrophil delivery or a leucine diet fine-tuned the immune balanceto enhance anti-PD-1 therapy in various murine cancer models. In summary, these datanot only indicate the neutrophil divergence across cancers but also suggest therapeutic opportunities such as antigen-presenting neutrophil delivery.
DOI: 10.1016/j.cell.2024.02.005
Source: https://www.cell.com/cell/abstract/S0092-8674(24)00126-0