Predicting how tumours will progress remains one of the central challenges in modern oncology. Researchers at the University of Geneva (UNIGE), working with colleagues from the Ludwig Institute for Cancer Research, have uncovered a mechanism showing how certain immune cells can be diverted to support, rather than suppress, cancer. Their work reveals that neutrophils — a highly abundant type of immune cell — are reprogrammed when they encounter the tumour environment and actively contribute to tumour growth. In this altered state, neutrophils begin producing the chemokine CCL3, a signalling molecule that encourages cancer progression instead of combating it. This process appears to represent a key variable in tumour biology and may serve as a valuable indicator of disease evolution. The findings have been published in the journal Cancer Cell.
Rather than being a simple mass of malignant cells, a tumour develops within a complex and dynamic ecosystem made up of many interacting cell types. Understanding which components of this environment truly influence tumour growth remains a major scientific difficulty. As Mikaël Pittet, full professor in the Department of Pathology and Immunology and at the Translational Research Centre in Onco-Haematology at UNIGE, explains, researchers are only beginning to decipher this intricate system. Identifying the elements that genuinely shape a tumour’s capacity to expand and evolve is essential if scientists are to predict its future behaviour.
Previous work by the same group had already demonstrated that the expression of two specific genes in macrophages is strongly associated with disease progression. This earlier discovery provided a relatively simple yet informative way to understand tumour trajectories. The new study introduces a second major variable, this time centred on neutrophils. By expanding their focus beyond macrophages, the researchers show that multiple immune cell populations can undergo changes that critically influence how cancer develops.
Neutrophils are among the most numerous cells in the immune system and normally serve as a rapid first line of defence against infections and tissue damage. In cancer, however, their presence is often linked to poorer outcomes. The researchers found that neutrophils drawn into the tumour environment experience a profound shift in their function. Instead of protecting the body, they begin producing CCL3 locally within the tumour, a molecule that actively promotes tumour growth. This reprogramming transforms neutrophils into allies of the cancer rather than its enemies.
Studying neutrophils presents substantial experimental and analytical challenges, as these cells are difficult to manipulate genetically and display low levels of gene expression. Evangelia Bolli, co-lead author of the study, describes how the team combined multiple experimental strategies to control CCL3 expression specifically in neutrophils without affecting other cell types. When CCL3 production was selectively turned off, neutrophils lost their tumour-promoting activity. Importantly, they continued to function normally in the bloodstream and were still able to accumulate within tumours, but no longer adopted the harmful reprogrammed state.
To strengthen their conclusions, the researchers revisited data from numerous independent studies using newly developed bioinformatics tools. Standard methods often fail to detect neutrophils accurately, but by refining analytical approaches, the team demonstrated that neutrophils across many cancer types follow a shared trajectory characterised by high CCL3 production. This pattern consistently correlates with pro-tumour activity. Together, these results position CCL3 as a promising prognostic marker and move researchers closer to defining a limited set of key variables that shape tumour evolution, opening the door to more precise and personalised cancer care.
More information: Evangelia Bolli et al, CCL3 is produced by aged neutrophils across cancers and promotes tumor growth, Cancer Cell. DOI: 10.1016/j.ccell.2026.01.006
Journal information: Cancer Cell Provided by Université de Genève
