Cancer sometimes shows a cruel irony: cells that are supposed to protect us can become adversaries. A recent discovery exposes how tumors manage to hijack a part of our immune defenses, turning certain allies into involuntary actors in the disease.
Neutrophils are very numerous white blood cells in the blood, occupying an important place in the rapid response to infections. Their presence normally indicates a protective action, but within a tumor, their behavior can take an unexpected direction, as reported in work conducted at the University of Geneva.
In the vicinity of a tumor, the environment is dense with immune cells and chemical signals. Researchers observe that neutrophils recruited to the site see their normal function altered, acquiring an activity that, instead of fighting it, favors the tumor.
This work, published in
Cancer Cell, identifies the chemokine CCL3 as a central factor in this reversal. Produced locally by the modified neutrophils, this molecule directly stimulates the growth of cancer cells.
Manipulating neutrophils represents a technical difficulty due to their short lifespan and fragility in the laboratory. The team developed methods to specifically control the expression of the CCL3 gene in these cells, demonstrating that in its absence, neutrophils lose their pro-tumor action while retaining their normal functions elsewhere.
These advances could help refine cancer prognosis. By integrating CCL3 into parameters already known, such as the expression of certain genes in macrophages, it becomes conceivable to better predict the evolution of the disease and imagine more personalized treatments for patients.
Tumor cells in light gray. Among the infiltrated neutrophils, some do not express CCL3 (blue), while others are positive for CCL3 (red).
Credit: Mikaël Pittet - UNIGE Chemokines, cellular messengers
Chemokines are small proteins produced by various cells, playing an important role in communication within the immune system. They function as chemical signals that guide immune cells to specific areas of the body, such as sites of infection or inflammation. This guiding function is essential for organizing an effective response against aggressions.
These molecules bind to specific receptors on the surface of target cells, inducing changes in their behavior, such as migration or activation. There is a great diversity of chemokines, each having distinct effects, which allows for precise regulation of cellular movements during immune processes.
During certain pathologies, chemokines can be diverted from their usual role. For example, in cancers, certain chemokines like CCL3 can be produced aberrantly.
Research on chemokines opens avenues for new therapies. By targeting these molecules or their receptors, it might be possible to modify the tumor environment or treat other inflammatory conditions, thus providing ways to interrupt deleterious signaling cascades while preserving beneficial immune functions.