Sydney scientists have watched, for the first time, immune cells quietly dismantling a living melanoma tumor—cell by cell—in real time. Researchers at the Garvan Institute of Medical Research used advanced microscopy to capture CD169-positive macrophages actively engulfing live cancer cells, a discovery that could reshape how Australia approaches treatment for one of its deadliest cancers.
The finding matters because melanoma kills thousands of Australians each year, yet we've long misunderstood one of our body's most powerful defenses. Macrophages—immune cells that make up as much as 30% of cells within a melanoma tumor—have been mysterious players in the cancer story. Scientists suspected they were doing more than we realized, but lacked the evidence. Now they have it: video footage of the cells at work.
Dr. Yuki Keith, first author of the research published in the Journal of Experimental Medicine, explains the significance: "This is the first time anyone has captured a macrophage attacking and engulfing a live cancer cell in real time. We always suspected macrophages were doing more than we gave them credit for—now we have the video footage to prove it."
The breakthrough came from recognizing that not all macrophages in the skin are the same. Keith's team identified a specific subpopulation expressing a protein called CD169. When they selectively depleted these CD169-positive macrophages in mice, tumors grew larger—proving these particular cells were holding cancer in check. The team then confirmed their findings in human tissue, finding CD169-positive macrophages present in healthy human skin and enriched around the margins of human melanoma tumors.
Using intravital two-photon microscopy, an advanced imaging technique that reveals cellular processes unfolding inside living organisms, the researchers observed these macrophages physically nibbling away and engulfing live melanoma cells, constraining tumor growth. As Professor Tri Phan, senior author on the paper, notes: "Macrophages have always been known as the body's housekeepers—they clear away dead cells and debris. What Dr. Keith caught on camera was these cells actively nibbling away and engulfing live cancer cells, constraining tumor growth."
What makes this discovery genuinely exciting is that the macrophages appear to attack cancer independently of T cells and B cells—the immune players most commonly credited with fighting cancer. This opens a new therapeutic door at a critical moment. Current immune checkpoint blockade therapy, which relies on T cells, has transformed advanced melanoma treatment, but only around half of patients respond. A major obstacle is the "cold tumor," which completely locks out T cells from the fight.
These housekeeping immune cells may offer a way forward. By understanding how CD169-positive macrophages work and potentially enhancing their function, researchers could develop new treatments for patients who don't respond to current therapies. For Australia, where melanoma rates remain among the highest in the world, this insight into the immune system's hidden army represents genuine hope—not just because of what we now see, but because of what we might finally be able to do about it.