World-First Footage Captures Macrophages Engulfing Live Melanoma Cells, Revealing New Therapeutic Avenue

For the first time in history, researchers have filmed immune cells actively attacking and consuming live cancer cells, a breakthrough that illuminates a previously underappreciated mechanism of tumor suppression and opens new possibilities for treating melanoma (搜索)搜索该疾病 and other solid tumors.

Scientists at the Garvan Institute of Medical Research查看公司主页 and UNSW Sydney employed intravital two-photon microscopy to observe CD169 (搜索)搜索该靶点-positive macrophages—immune "housekeeper" cells—engulfing live B16-F10 melanoma (搜索)搜索该疾病 cells in real time in mouse models. The findings, published in the Journal of Experimental Medicine, identify a macrophage subpopulation that constrains tumor growth independently of the adaptive immune system.

"This is the first time anyone has captured a macrophage attacking and engulfing a live cancer cell in real time," said Dr. Yuki 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."

A Distinct Macrophage Population with Direct Anti-Tumor Activity

Macrophages can account for up to 30 percent of the cells within a melanoma (搜索)搜索该疾病 tumor, yet their precise role in either promoting or suppressing tumor growth has remained elusive. The Garvan team focused on a subpopulation expressing CD169 (搜索)搜索该靶点, a protein known to facilitate antigen presentation to B cells and T cells and previously associated with better prognosis in cancer patients.

Using mice injected with B16-F10 melanoma (搜索)搜索该疾病 cells expressing the red fluorescent protein mCherry, the researchers demonstrated through intravital microscopy and immunofluorescence that CD169 (搜索)搜索该靶点-positive macrophages directly phagocytose live tumor cells. When the team selectively depleted these macrophages—including in mice engineered to lack T and B cells—tumor growth became unrestrained.

Flow cytometry on tumor-infiltrating leukocytes confirmed that the macrophages control tumors independent of T and B cells. Professor Tri Phan, senior author on the paper, described this finding as "unexpected, and genuinely exciting," noting that T and B cells are "the immune players most commonly credited with fighting cancer."

Human Relevance Confirmed

To establish translational relevance, researchers at Melanoma Institute Australia查看公司主页 analyzed skin biopsies from human patients via immunostaining. The analysis revealed that CD169 (搜索)搜索该靶点-positive macrophages are enriched in the hypodermis—the innermost layer of skin—in both healthy and melanoma (搜索)搜索该疾病 tissues, and concentrate around the edges of melanoma tumors.

Implications for Immunotherapy and Cold Tumors

The discovery carries significant implications for cancer immunotherapy. Immune checkpoint blockade, which depends on T cells to identify and destroy cancer cells, has transformed treatment for advanced melanoma (搜索)搜索该疾病. However, only about half of patients respond, partly due to "cold tumors" that prevent T cell infiltration.

"While macrophages are known as the body's housekeepers, they also have a second job: acting as immune informants," Dr. Keith 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 (搜索)搜索该靶点-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 tumor to finish the job."

A Mobilizable Immune Army

The researchers now aim to determine precisely how CD169 (搜索)搜索该靶点-positive macrophages interact with T cells, with the goal of developing therapies that could complement existing immunotherapies.

"If we can harness this population of macrophages, we potentially have an immune army already in place, ready to be mobilized," said Professor Phan. "Future treatments could involve developing targeted drugs that boost their numbers, or make them 'hungrier' or better at tagging cancer cells for killing. By combining this approach with existing therapies, we could potentially make immunotherapy work for a much larger group of patients."

The approach may extend well beyond melanoma (搜索)搜索该疾病. As Professor Phan noted, macrophages are highly abundant in most solid tumors, suggesting broad applicability across cancer types.

The research was supported by Australia's National Health and Medical Research Council, the Australian Cancer Research Foundation, Cancer Institute New South Wales, The Angles Family Foundation, Tour de Cure, and the 2025 Jacqueline Goodnow & Hartley Prize. Melanoma (搜索)搜索该疾病 biopsy samples were provided and analyzed by Melanoma Institute Australia查看公司主页.