We have the video footage to prove it.
Inside living tissue, for the first time, scientists have witnessed the body doing something it has quietly done all along — immune cells called macrophages consuming live cancer cells in real time. Researchers at the Garvan Institute and UNSW Sydney identified a specific subpopulation of these cells, marked by the protein CD169, that actively restrains melanoma growth independent of the immune system's better-known defenders. The discovery reframes a long-misunderstood cellular actor and opens a path toward treating the roughly half of melanoma patients whose tumors remain invisible to current immunotherapy.
- Advanced microscopy has captured, for the first time in a living organism, immune cells physically engulfing and destroying live melanoma tumor cells — not in simulation, but in real biological time.
- The finding disrupts decades of confusion: macrophages were long suspected of either helping or enabling tumors, but isolating the CD169-positive subpopulation revealed they are in fact active suppressors of cancer growth.
- The urgency sharpens around 'cold tumors' — cancers that wall out T cells entirely, leaving half of all melanoma patients with no meaningful response to the immunotherapies that have otherwise transformed treatment.
- Macrophages may serve as biological messengers, breaking down cancer cells and displaying warning fragments that recruit T cells into the fight, suggesting a communication bridge that current therapies have never tried to cross.
- The next research phase aims to decode exactly how CD169-positive macrophages signal to T cells — a conversation that, if amplified therapeutically, could extend immunotherapy's reach across melanoma and potentially many other solid tumors.
For the first time, scientists have watched immune cells consume living cancer cells inside a living organism. Using advanced intravital microscopy, researchers at the Garvan Institute of Medical Research and UNSW Sydney filmed macrophages physically engulfing melanoma cells in real time — a mechanism the body has long employed against one of Australia's deadliest cancers, but one that science had largely passed over.
Macrophages account for roughly 30 percent of cells within a melanoma tumor, and their role has long been contested — were they fighting the cancer or feeding it? Previous attempts to answer this by removing all macrophages produced inconclusive results. Dr. Yuki Keith's team took a more precise approach, identifying a specific subpopulation marked by the protein CD169. When only these cells were selectively eliminated, tumors grew larger. The implication was clear: CD169-positive macrophages were actively holding cancer in check.
What made the discovery stranger and more significant was that these macrophages appeared to operate independently of T cells and B cells — the immune system's celebrated frontline fighters. Current melanoma treatment works by unleashing T cells against tumors, and it has transformed outcomes for many patients. But roughly half don't respond, because their tumors manage to exclude T cells entirely, creating what immunologists call a 'cold tumor.'
Macrophages, however, do more than consume threats. After engulfing a cancer cell, they break it down and display molecular fragments on their surface — biological warning flags that may recruit T cells into the fight. If CD169-positive macrophages are doing exactly this, they could serve as a bridge into cold tumors that T cells alone cannot enter.
The therapeutic possibilities are substantial. Boosting macrophage numbers, enhancing their aggression, or improving their ability to tag cancer cells for destruction could extend immunotherapy's reach to patients currently left behind. And because macrophages are abundant across most solid tumors, the implications stretch well beyond melanoma — toward a broader, more inclusive arsenal against cancer.
For the first time, scientists have watched immune cells actively consume living cancer cells—not in a petri dish or a computer model, but inside a living organism. Researchers at the Garvan Institute of Medical Research and UNSW Sydney used advanced microscopy to capture macrophages, a type of immune cell, physically engulfing melanoma cells in real time. The footage, published in the Journal of Experimental Medicine, reveals a mechanism the body has been using all along to fight one of Australia's deadliest cancers, one that researchers had largely overlooked.
Macrophages make up roughly 30 percent of the cells inside a melanoma tumor. Scientists have known for years that these "housekeeping" immune cells exist in tumors, but there has been genuine confusion about whether they help or hurt the cancer's growth. Previous research attempted to answer this by simply removing all macrophages from the body and observing what happened. The results were murky. Dr. Yuki Keith and her team took a different approach. They discovered that not all macrophages are created equal. One specific subpopulation—cells marked by a protein called CD169—turned out to be the crucial players. When the researchers selectively eliminated these CD169-positive macrophages, tumors grew larger. This single finding flipped the script: these cells were actively restraining cancer growth.
Using intravital two-photon microscopy, an imaging technique that allows researchers to observe cellular-level processes inside living animals, the team watched CD169-positive macrophages attack and consume live melanoma cells. To verify this wasn't just a quirk of mouse biology, they examined human tissue samples and found the same macrophages present in healthy human skin and concentrated around the edges of human melanoma tumors. The discovery carried an unexpected twist: these macrophages appeared to be doing their work independently of T cells and B cells, the immune system's most celebrated cancer fighters. This independence matters enormously.
Current melanoma treatment relies heavily on immune checkpoint blockade therapy, which essentially removes the brakes on T cells so they can hunt down cancer. The approach has transformed outcomes for advanced melanoma patients—but only about half respond to it. The other half face what immunologists call a "cold tumor," a tumor that somehow manages to exclude T cells entirely, leaving them untouched by the therapy. Here is where the macrophage discovery becomes clinically significant. Macrophages do more than simply consume threats; they also act as messengers. After engulfing a pathogen or cancer cell, they break it down and display fragments on their surface like biological warning flags. The researchers suspect that CD169-positive macrophages are doing exactly this with live cancer cells, potentially signaling to T cells that a threat exists and needs to be eliminated.
If that hypothesis holds, it opens a new therapeutic avenue. Rather than relying solely on T cells to find and destroy cancer, doctors could potentially amplify the macrophage population, make them more aggressive, or enhance their ability to tag cancer cells for destruction. Combining such an approach with existing immunotherapies could extend treatment success to patients who currently don't respond. The implications stretch beyond melanoma. Macrophages are abundant in most solid tumors, meaning this mechanism could apply to many cancers. The next phase of research will focus on understanding exactly how CD169-positive macrophages communicate with T cells—the conversation that could unlock a much larger arsenal against cancer.
Notable Quotes
We always suspected macrophages were doing more than we gave them credit for – now we have the video footage to prove it.— Dr. Yuki Keith, UNSW Conjoint Senior Lecturer and first author
If we can harness this population of macrophages, we potentially have an immune army already in place, ready to be mobilised.— Prof. Tri Phan, senior author
The Hearth Conversation Another angle on the story
Why does it matter that researchers watched this happen in a living system rather than in a lab dish?
Because a tumor isn't just cancer cells sitting in isolation. It's an ecosystem—immune cells, blood vessels, connective tissue all interacting. A petri dish can't capture that complexity. Seeing macrophages attack cancer cells inside a living mouse shows you what's actually happening in the body, not a simplified version of it.
You mentioned these CD169-positive macrophages work independently of T cells. Why is that surprising?
For decades, immunotherapy has been built on the idea that T cells are the main soldiers fighting cancer. Everything else was treated as supporting cast. Finding that macrophages can actively consume cancer cells on their own, without waiting for T cells to show up, suggests the immune system has multiple independent strategies we haven't fully exploited.
What's a "cold tumor" and why does it matter here?
A cold tumor is one that T cells can't penetrate or don't recognize as a threat. Current immunotherapy essentially doesn't work on cold tumors because it depends on T cells doing the killing. But if macrophages are already inside the tumor, already eating cancer cells, and already tagging them for immune recognition, you have a potential entry point that doesn't require T cells to arrive first.
So the next step is figuring out how macrophages talk to T cells?
Exactly. If researchers can understand that conversation—how macrophages signal to T cells that cancer is present—they could potentially amplify it. You could design drugs that make macrophages more numerous, more aggressive, or better at flagging cancer cells. Then combine that with existing therapies.
How far away is that kind of treatment?
The science is still early. They've proven the mechanism exists and matters. Now comes the harder work of translating that into drugs that actually work in patients. That typically takes years, but the foundation is solid.