Researchers at the University of Geneva have discovered that tumors can reprogram neutrophils, turning these immune cells from defenders against infection into promoters of cancer growth through the production of a molecule called CCL3. This finding, published in Cancer Cell, suggests CCL3 could serve as a marker for tracking tumor progression across various cancers. The study highlights how the tumor environment alters immune responses to favor disease advancement.
Cancer research continues to unravel the complex interactions within tumors that enable their growth and spread. A study led by Mikaël Pittet, professor in the Department of Pathology and Immunology at the University of Geneva (UNIGE) and a member of the Ludwig Institute for Cancer Research, reveals a key mechanism involving neutrophils.
Neutrophils, typically the body's first responders to infection and injury, often correlate with poorer outcomes in cancer patients. The research shows that tumors recruit these cells and expose them to an environment that reprograms their function. As Pittet explains, "We discovered that neutrophils recruited by the tumor undergo a reprogramming of their activity: they begin producing a molecule locally -- the chemokine CCL3 -- which promotes tumor growth."
This reprogramming shifts neutrophils from protective roles to supporting tumor progression. The team faced significant challenges in studying neutrophils due to their resistance to genetic manipulation. Co-lead author Evangelia Bolli, a former postdoctoral researcher at UNIGE, noted, "Neutrophils are particularly difficult to study and to manipulate genetically." By combining experimental strategies, the researchers specifically controlled CCL3 expression in neutrophils. Removing CCL3 prevented the cells from aiding tumor growth, though they still accumulated in tumors and functioned normally in the bloodstream.
To validate their findings, the team analyzed data from multiple independent studies, developing new methods to detect neutrophils, which are often overlooked in standard analyses. Co-first author Pratyaksha Wirapati stated, "We had to innovate to detect neutrophils more accurately." The analysis confirmed that in many cancers, these cells produce high levels of CCL3, linking it to pro-tumor activity.
Pittet emphasized the broader implications: "We are deciphering the 'identity card' of tumors, by identifying, one by one, the key variables that determine the evolution of the disease." This builds on prior work from 2023 on macrophages and points toward personalized cancer management. The study was published in Cancer Cell with the DOI: 10.1016/j.ccell.2026.01.006.
