A novel role of neutrophils in combating cancer, finds research

Using cutting-edge single-cell RNA sequencing technology, the researchers analysed individual neutrophils across a remarkable 17 different cancer types from 143 patients and revealed that neutrophils can adopt at least 10 highly specialized and distinct functional states related to inflammation, blood vessel formation, and—most excitingly—presenting antigens to activate potent cancer-killing T cells.

"We were surprised to find such intricate complexity and divergent roles embedded within neutrophils, which have been overlooked for so long as a simple population," said Prof. ZHANG Xiaoming from the Shanghai Institute of Immunity and Infection (SIII) of the Chinese Academy of Sciences. "What is especially remarkable is their newly discovered capacity to act as antigen-presenting cells, maturing and rallying T cells against cancer. In addition, the abundance of antigen-presenting neutrophils is associated with improved patient prognosis across many tumour types revealed in this study."

After extensive analysis, researchers discovered that metabolic signalling of the amino acid leucine can activate the antigen-presenting state in neutrophils, leading to epigenetic changes. Validating these findings in vivo, they observed that delivering antigen-presenting neutrophils or adjusting the leucine diet significantly enhanced the anti-tumour immune response in mice. Moreover, these treatments notably improved outcomes of PD-1 checkpoint immunotherapy for various cancer types.

“We've uncovered a way to wake up an untapped army already living within our immune system. Strategically activating these neutrophil states or modulating their behaviour through metabolic or dietary means represents an entirely new paradigm to empower cancer immunotherapy,” said Prof. ZHANG.

"This completely changes how we perceive neutrophils in the context of cancer," said Profs. GAO Qiang from Fudan University. "Now we know we could harness the diverse hidden identities of neutrophils to strengthen the effectiveness of immunotherapies. We're thrilled to further explore the potential benefits of these newly uncovered mechanisms in clinics."

Reference: Yingcheng Wu, Jiaqiang Ma, Xupeng Yang , Jia Fan, Xiaoming Zhang, Qiang Gao; Journal: Cell; DOI: 10.1016/j.cell.2024.02.005