A recent research study led by A*STAR’s Singapore Immunology Network (A*STAR.SIgN) has revealed a significant transformation in neutrophils, one of the most prevalent white blood cells in our body, within specific cancers. These neutrophils undergo notable changes, adopting a novel function that actively supports tumor growth. Through a meticulous examination of neutrophils upon their entry into the tumor, scientists from A*STAR.SIgN has identified ways to accurately distinguish tumor-promoting neutrophils from their normal counterparts elsewhere in the body. Neutrophils, indispensable in fighting infections, play vital roles, and their depletion due to chemotherapy often leaves cancer patients susceptible to potentially fatal infections.
By honing the capability to distinctly identify tumor-promoting neutrophils, a groundbreaking avenue emerges for targeting tumors while safeguarding the normal neutrophil response. The study, titled “Deterministic reprogramming of neutrophils in tumors,” was published in Science on January 12, 2024.
Neutrophils, recognized as the immune system’s initial responders, swiftly migrate from the bloodstream into tissues to combat disease-causing pathogens. In cancer, previous scientific findings have highlighted the pivotal role of various neutrophil types within tumors, contributing to tumor growth and subsequently leading to poorer clinical outcomes in cancer patients. However, the mechanism of generation and cooperative interactions among these distinct neutrophil types remained unclear, hindering the precise targeting of tumor-promoting neutrophils.
In response to this challenge, a group of scientists from A*STAR.SIgN employed an experimental pre-clinical model of pancreatic cancer. They demonstrated that various types of neutrophils acquired novel characteristics and functions upon migration into the tumor—a process termed “reprogramming.” Neutrophils undergoing this reprogramming were consolidated into a unified population, irrespective of their initial origins. By meticulously tracking this reprogramming process, the team could investigate how these modified neutrophils facilitated sustained tumor growth.
Reprogrammed neutrophils were found to stimulate the growth of new blood vessels within the tumor’s core, likely aiding the tumor in overcoming restricted access to oxygen and nutrients. Blocking this vessel-promoting function or removing reprogrammed neutrophils from interaction with the tumor resulted in a reduction in the growth of pancreatic tumors in pre-clinical models.
Upon re-analyzing other published human datasets, the team identified similar instances of neutrophil reprogramming, suggesting a shared pathway where neutrophils could be similarly modified to promote tumor growth in specific solid cancers. Consequently, this study holds promise for future therapeutic strategies in cancer that target neutrophil reprogramming and their subsequent functions, complementing existing treatments and immunotherapies designed to activate the immune system for tumor eradication.
Executive Director Rof Lam Kong Peng of A*STAR.SIgN expressed, “Pioneering scientific advancements, exemplified by this study led by A*STAR.SIgN, are pivotal as they empower us to forge the next era of cancer immunotherapeutics, ultimately enhancing clinical outcomes for Singapore and its citizens.”
The team aims to delve deeper into understanding the factors behind neutrophil reprogramming in human cancers. This pursuit is essential for devising more efficacious methods to target and treat cancer, emphasizing strategies centered around neutrophils.
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