Pro-inflammatory M1 macrophages induce an inflammatory, invasive phenotype in melanoma cells

Melanoma cells with the cell membrane protein CD44 stained in red and the nucleus in blue. Dil-labelled extracellular vesicles taken up by cancer cells are shown in green. Image by Kaisa Mäki-Mantila.

Pro-inflammatory macrophages may do more than mark an inflamed tumour microenvironment; they may help drive melanoma toward a more invasive phenotype, according to new data from the University of Eastern Finland. The findings, published in Cell Communication and Signaling, position macrophage-derived extracellular vesicles as active agents in melanoma progression rather than passive bystanders of chronic inflammation.​

In the study, investigators focused on extracellular vesicles secreted by classically activated, pro-inflammatory M1 macrophages and their effects on melanoma cells in vitro. These small membrane-bound particles, long recognized as mediators of intercellular communication, appear to have a particularly prominent role within the tumour microenvironment, where immune and malignant cells are in continuous molecular dialogue. A high intratumoural macrophage count has previously been associated with poor prognosis in melanoma and other malignancies, but the mechanisms underpinning this association have remained only partially understood.​

The researchers report that extracellular vesicles released by M1 macrophages are enriched with inflammatory mediators, including cytokines TNFα and IL-1β, which are efficiently delivered into melanoma cells via vesicular transfer. Once internalized, these vesicles activate the NF-κB signalling pathway in target cells, amplifying pro-inflammatory transcriptional programs that are central to many cancer-related processes. The resulting milieu was associated with enhanced aggressiveness and invasiveness, as melanoma cells acquired increased motility and a greater capacity to penetrate surrounding tissue in experimental models.

“‘We showed that extracellular vesicles secreted by M1 macrophages can enhance melanoma cell motility and, as a result, melanoma progression,” said doctoral researcher Kaisa Mäki-Mantila of the University of Eastern Finland in a press release. “They enhance inflammatory signals within the tumour microenvironment and create a favourable, self-sustaining inflammatory cycle for cancer cells to thrive in.”

The research suggests that interrupting this vesicle-mediated crosstalk could represent a novel therapeutic strategy. By identifying a discrete, targetable conduit through which macrophages and melanoma cells reinforce a pro-tumour inflammatory circuit, the study opens the door to approaches aimed at either modifying vesicle cargo, blocking vesicle uptake, or dampening downstream NF-κB activation within malignant cells.