Revealing Neutrophils’ Unexpected Diversity
A groundbreaking study published in Cell on March 5th by Prof. Zhang Xiaoming from the Shanghai Institute of Immunity and Infection (SIII) of the Chinese Academy of Sciences, along with Profs. Gao Qiang, Fan Jia, and Yang Li from Fudan University, has unveiled an unexpected level of complexity within neutrophils. Previously considered a relatively uniform population of short-lived immune cells, they have now been revealed to possess remarkable diversity and specialized functional states.
Using state-of-the-art single-cell RNA sequencing technology, the researchers examined individual neutrophils across 17 different cancer types from 143 patients. Contrary to previous beliefs, they discovered that it can adopt at least 10 highly specialized and distinct functional states. These states are involved in processes such as inflammation, blood vessel formation, and, most notably, presenting antigens to activate potent cancer-killing T cells.
Harnessing Neutrophils’ Potential in Cancer Immunotherapy
Prof. Zhang Xiaoming expressed surprise at the intricate complexity found within neutrophils, emphasizing their newfound capacity as antigen-presenting cells. Additionally, the abundance of antigen-presenting neutrophils was linked to improved patient prognosis across various tumor types. The researchers identified metabolic signaling of the amino acid leucine as a key factor in activating this antigen-presenting state, leading to significant epigenetic changes.
Through further analysis, the team determined that strategically activating these neutrophil states or modulating their behavior through metabolic or dietary means could revolutionize cancer immunotherapy. In vivo models validated the therapeutic potential of these findings, 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 outcomes of PD-1 checkpoint immunotherapy across different cancer types.
Implications for Cancer Diagnosis and Treatment
Prof. Gao Qiang highlighted the transformative impact of these discoveries, emphasizing the potential to harness the diverse identities of neutrophils to strengthen immunotherapies. The study underscores the value of single-cell sequencing approaches in uncovering new functional dimensions within immune cells. By tapping into the hidden potential, researchers aim to gain new insights into cancer diagnosis and treatment, offering hope for more effective and personalized therapeutic strategies in the future.
