Scientists capture 'housekeeping' immune cells attacking live melanoma

by Garvan Institute of Medical Research

edited by Sadie Harley, reviewed by Robert Egan

Sadie Harley

Scientific Editor

Meet our editorial team
Behind our editorial process

Robert Egan

Associate Editor

Meet our editorial team
Behind our editorial process Editors' notes

This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility:

fact-checked

peer-reviewed publication

trusted source

proofread

The GIST Add as preferred source

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 the way 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 tumors, steadily engulfing cancer cells and slowing tumor growth.

"This is the first time anyone has captured a macrophage attacking and engulfing a live cancer cell in real time," says Dr. Yuki Keith, first author of the research.

"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 the treatments of the future."

A hidden army in the skin

Macrophages are a type of immune cell that makes up as much as 30% of the cells within a melanoma tumor. While they have long been known to play a role in cancer, there has been little clarity around whether they help or hinder tumor growth.

In the past, researchers have tried indiscriminately eliminating all the macrophages in the body to see how it affects the tumor.

However, Dr. Keith's team found that not all macrophages in the skin were the same, identifying one particular subpopulation that expressed a protein called CD169. By specifically targeting and depleting these CD169-positive macrophages, they found the tumors grew larger. This shows that these specific macrophages were preventing the melanoma from growing.

Watching cancer cells being eaten in real time

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

To confirm the clinical relevance of their real-time footage, the team also analyzed human tissue, finding these same macrophages present in healthy human skin and enriched around the margins of human melanoma tumors.

"Macrophages have always been known as the body's housekeepers—they clear away dead cells and debris," explains Professor Tri Phan, senior author on the paper.

"What Dr. Keith caught on camera was these cells actively nibbling away and engulfing live cancer cells, constraining tumor growth. 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."

Implications for immunotherapy

This independent first strike has big implications for immunotherapy. Immune checkpoint blockade therapy, which relies on T cells to seek out and destroy cancer cells, has transformed the treatment of advanced melanoma—but currently only around half of patients respond, necessitating more effective treatments. A major hurdle is the so-called immune "cold tumor"—a tumor that completely locks out T cells.

"While macrophages are known as the body's housekeepers, they also have a second job: acting as immune informants," Dr. Keith explains.

"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 tumor to finish the job."

The team's next step is to understand exactly how these CD169-positive macrophages communicate with T cells.

"If we can harness this population of macrophages, we potentially have an immune army already in place, ready to be mobilized," says 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. This could also apply to many cancers beyond melanoma, as macrophages are highly abundant in most solid tumors."

Publication details

1 CSF1R-dependent CD169-positive macrophages locally constrain melanoma growth in the skin, Journal of Experimental Medicine (2026). DOI: 10.1084/jem.20252239

Journal information: Journal of Experimental Medicine

Key medical concepts

MacrophagesMelanomaCheckpoint Blockade Immunotherapy

Clinical categories

OncologyAllergy and immunology Provided by Garvan Institute of Medical Research Who's behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries. Full profile →

Robert Egan

Bachelor's in mathematical biology, Master's in creative writing. Well-traveled with unique perspectives on science and language. Full profile →

Citation: Scientists capture 'housekeeping' immune cells attacking live melanoma (2026, May 21) retrieved 22 May 2026 from https://medicalxpress.com/news/2026-05-scientists-capture-housekeeping-immune-cells.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.