Macrophages Captured Attacking Live Melanoma Cells in Breakthrough Immune Discovery

Quick summary: Pioneering oncology research from the Garvan Institute of Medical Research has captured real time video footage of CD169 positive macrophage immune cells actively engulfing live melanoma cells, identifying an independent frontline mechanism that naturally constrains solid tumour growth. Advanced microscopic tracking demonstrates that these specialized cells, which comprise up to 30% of melanoma tumours, act as vital immune informants by physically tagging cancer threats to potentially recruit dormant T cells into immunologically cold environments. These biological insights carry profound implications for public policy and healthcare practice, offering a revolutionary dual therapy framework that could double the efficacy rates of existing cancer treatments and dramatically improve survival outcomes for patients facing advanced malignancies.

Scientists at the Garvan Institute of Medical Research have captured, for the first time, “housekeeping” immune cells actively attacking and engulfing live melanoma cells, a discovery that could change how we approach treatment for one of Australia’s most common and deadly cancers.

The findings, published in the Journal of Experimental Medicine, reveal a previously overlooked population of immune cells called macrophages that patrol the edges of melanoma tumours, steadily engulfing cancer cells, and slowing tumour growth.

Macrophages make up as much as 30% of the cells in a melanoma tumour. While they have long been known to play a role in cancer, there has been little clarity around whether they help or hinder tumour growth. Past researchers tried indiscriminately eliminating all macrophages in the body to observe the effect on tumours.

Dr Yuki Keith’s team took a different approach, identifying one particular subpopulation of skin macrophages that expressed a protein called CD169. By specifically targeting and depleting these CD169-positive macrophages, they found that tumours grew larger, confirming that this subpopulation was actively preventing melanoma growth.

Using intravital two-photon microscopy, an advanced imaging technique that allows researchers to watch biological processes unfold at the cellular level inside living organisms, the team observed CD169-positive macrophages physically engulfing live melanoma cells in mice.

“This is the first time anyone has captured a macrophage attacking and engulfing a live cancer cell in real time,” said Dr Keith, first author of the study. “We always suspected macrophages were doing more than we gave them credit for, now we have the video footage to prove it. Studying this in a living system is crucial because it is more representative of what happens in real life, showing the complexity of the immune system, and paving the way for future treatments.”

To confirm the clinical relevance of their findings, collaborators at Melanoma Institute Australia analysed human tissue and found the same macrophages present in healthy human skin, and enriched around the margins of human melanoma tumours.

“What Dr Keith captured on camera was these cells actively nibbling away and engulfing live cancer cells, constraining tumour growth,” said Professor Tri Phan, senior author on the paper. “Critically, this attack appears to occur independently of T cells and B cells, the immune players most commonly credited with fighting cancer, which made the discovery unexpected, and genuinely exciting.”

This independent mechanism has significant implications for immunotherapy. Immune checkpoint therapy, which relies on T cells to seek out and destroy cancer cells, has transformed treatment of advanced melanoma, but currently only around half of patients respond to it. A major hurdle is the so-called “cold tumours,” one that completely locks out T cells.

Dr Keith believes CD169-positive macrophages could be key to solving this problem. “While macrophages are known as the body’s housekeepers, they also have a second job: acting as immune informants,” she explained. “Once they consume a threat, they chew it up and display a piece of it on their surface, like a biological red flag. We suspect that these CD169-positive macrophages are doing exactly this with the live cancer cells, which means they could hold the key to calling the T cell cavalry into the tumour to finish the job.”

The team’s next step is to understand exactly how CD169-positive macrophages communicate with T cells, with future treatments potentially including targeted drugs that boost the numbers of these macrophages, make them more effective at engulfing cancer cells, or enhance their ability to tag cancer cells for destruction by T cells.

“If we can harness this population of macrophages, we potentially have an immune army already in place, ready to be mobilised,” said Professor Phan. “By combining this approach with existing therapies, we could make immunotherapy work for a much larger group of patients. This could also apply to many cancers beyond melanoma, as macrophages are highly abundant in most solid tumours.”

Researchers emphasise that further studies are needed to translate these findings into clinical applications, but the real-time visualisation provides compelling evidence of an underappreciated frontline defence in the skin’s immune system.