Prof. Zhang Xiaoming from the Shanghai Institute of Immunity and Infection (SIII) at the Chinese Academy of Sciences, along with Profs. Gao Qiang, Fan Jia, and Yang Li from Fudan University, have unveiled a previously unrecognized complexity within neutrophils. Neutrophils were traditionally considered a relatively uniform population of short-lived immune cells, but the researchers, utilizing advanced single-cell RNA sequencing technology, discovered a surprising diversity.

By analyzing individual neutrophils from 143 patients across 17 different cancer types, the team identified at least 10 highly specialized and distinct functional states of neutrophils. These states were associated with various functions, including inflammation, blood vessel formation, and, notably, presenting antigens to activate powerful cancer-killing T cells.

The researchers further revealed that the antigen-presenting state in neutrophils could be triggered through metabolic signaling involving the amino acid leucine, leading to subsequent epigenetic changes. Prof. Zhang expressed the significance of this discovery, stating, “We’ve uncovered a way to awaken an untapped army within our immune system. Strategically activating these neutrophil states or modulating their behavior through metabolic or dietary means represents a revolutionary approach to enhancing cancer immunotherapy.”

Validation of these findings was conducted through in vivo models, demonstrating that delivering antigen-presenting neutrophils or adjusting the leucine diet significantly enhanced the anti-tumor immune response in mice. Moreover, these treatments markedly improved the outcomes of PD-1 checkpoint immunotherapy across various cancer types.

Prof. Gao highlighted the transformative impact of this research on our understanding of neutrophils in the context of cancer, emphasizing the potential to harness their diverse identities to bolster the effectiveness of immunotherapies. The study underscores the importance of single-cell sequencing approaches in unveiling new functional dimensions within seemingly well-understood immune cells. Exploring the hidden potential of neutrophils may offer fresh insights into cancer diagnosis and treatment.

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