Macrophages (green) engulfing melanoma cells (purple). Keith et al. / Garvan Institute, CC BY-SA Yuki Keith, Garvan Institute and Tri Phan, Garvan Institute

For the past 15 years or so, a class of drugs called immune checkpoint inhibitors have been used to treat melanoma – the most dangerous kind of skin cancer.

For many patients, they produce remarkable results. For others, they do nothing.

We still don’t really know why. But in new research published in the Journal of Experimental Medicine, we observed immune cells called macrophages attacking melanoma cells in real time – which may offer clues about how we can make those therapies work for all patients, not just some.

Tumours, hot and cold

One of us (Yuki) treated patients with melanoma in Japan as a dermatologist. The other (Tri Phan) runs a lab at the Garvan Institute in Sydney, where his team specialises in observing the cells of the immune system in real time.

When Yuki wanted to understand why immune checkpoint inhibitors were failing for many patients, she joined Tri Phan’s lab to continue her research.

The treatment fails in what oncologists call “cold” tumours, where the cancer’s environment actively prevents a kind of immune cell called a T cell attacking it. One of our lab’s aims is trying to work out how to make the tumours “hot”, allowing T cells to penetrate and destroy the cancer cells.

Our new findings suggest a different kind of immune cell, called macrophages, may hold the key.

Macrophages (green) engulfing melanoma cells (purple). Yuki Keith, CC BY

The housekeepers we’ve been ignoring

In 1908, Russian zoologist Ilya Mechnikov was awarded a Nobel Prize for the discovery of phagocytosis (“cell eating”) in the immune system, which is carried out by cells he called macrophages (from the Greek for “big eaters”).

These cells engulf and clear away the debris caused by tissue damage and cell death. They are often regarded as the body’s silent, no-fuss housekeepers.

However, their role in cancer has often been overlooked. Unlike other immune cells that move through the blood and patrol the whole body, macrophages are “tissue-resident” and stay in one place.

A microscopic view of a melanoma tumour growing in the skin shows CD169 macrophages in green and yellow forming a biological boundary wall around the tumour. Keith et al. / Garvan Institute, CC BY

Earlier studies of the role of macrophages in cancer assumed these housekeepers were all the same. But when we looked closely in the skin, it became clear that there were many different kinds of macrophages living in different layers.

One particular kind of macrophages (recognised by a protein called CD169) lives in a deeper part of the skin, called the hypodermis.

We found that these macrophages arranged themselves around the edges of a melanoma tumour, as if they were trying to wall it off. When we depleted the macrophages, the melanomas grew bigger, suggesting they were constraining the growth of the tumours.

Watching cancer cells being eaten alive

To understand what these CD169-positive macrophages were actually doing, we used an advanced imaging technique called intravital two-photon microscopy. This allows us to watch biological processes unfold in living tissue in real time.

What we saw was surprising: the macrophages were “nibbling” and actively engulfing live melanoma cells. While we had seen macrophages eat dead cells in our lab before, we had never seen them eat a live melanoma cell in a model organism.

What was even more surprising was that this immune attack was happening without the need for T cells, or antibodies made by another kind of immune cell called B cells – the immune players most commonly credited with fighting cancer.

We also confirmed this is not something that just happens in the lab. Our colleagues at the Melanoma Institute Australia analysed samples from human melanoma patients and found similar populations of CD169-expressing macrophages on the edges of the tumour, suggesting they may play a similar protective role there.

Calling in the cavalry – implications for therapies

Macrophages don’t just clear away debris. They can also alert the immune system to danger. After they have digested the debris, they can display it like a biological “red flag” to direct T cells to find and kill the cancer cells.

What makes a macrophage decide whether to silently dispose of debris without alerting the immune system, or wave the red flags to activate the immune system, is still unclear. Because the CD169-expressing macrophages are strategically positioned around the tumours, we suspect they may hold the key.

Macrophages are widespread in most solid tumours – including glioblastoma, breast cancer and many others. This is an army already in place waiting to be mobilised.

Our next step is to understand precisely how these macrophages eat live cancer cells and how they can communicate the danger to T cells, so we can harness this population with new treatments.

Yuki Keith, Postdoctoral Researcher, Immunology, Garvan Institute and Tri Phan, Program Director – Precision Immunology / Laboratory Head, Garvan Institute

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Read More........→May 27, 2026 Categories: Health,Research

Daniel Joyce, University of Southern Queensland

I heard that we see upside down, but our brain flips the image. How does it do that?

–Jasmine, Mount Evelyn, Victoria

Our eyes work thanks to light. Objects we can see are either sources of light themselves – like a candle or a phone screen – or light bounces off them and makes its way to our eyes.

First, light passes through the optical components of the eyes such as the cornea, pupil and lens.

Together, they help focus the light onto the retina that senses light, while also controlling the intensity of light to help us see well while avoiding damage to the eye.

The function of the lens is to correctly focus light that comes from objects at different distances. This process is known as accommodation.

While performing this important task, light passing through the lens becomes inverted. This means that light from the top of the object falls lower on the retina than light from the bottom, which falls higher on the retina.

So, light exiting the lens to land on the retina is indeed flipped upside down. But that doesn’t mean the brain is actually flipping the picture “back”. Here’s why.

The orientation doesn’t actually matter

While the light being interpreted by the brain is “upside down” compared to the real world, the question is: is that actually a problem for us?

From your own experience you can tell the answer is probably no. We seem to navigate and interact with the world just fine.

So, where in the brain is the image flipped or rotated 180 degrees to be the “right way up” again?

You may be surprised to learn that vision scientists reject the idea a flipping or rotation needs to happen at all. This is because of how our brains process visual information.

The object you perceive is “encoded” by the firing of various neurons – brain cells that process information – in various locations in the brain. This pattern of firing is what encodes the information about the object you’re focusing on. That info takes into account the object’s relation to everything else in the scene, your body in the world, and your movements.

As long as the relative encodings of these are all consistent with one another, as well as stable, there’s no need for a flip to happen at all.

We can function with ‘upside down’ goggles!

Several studies have looked at how we adapt to large changes in visual input by asking people to wear goggles that flip the image coming in.

This means the image lands on the retina the “right way up”, so to speak, but upside down from what the brain has learned it should be.

In the 1930s, two scientists in Austria performed the Innsbruck Goggle Experiments. For weeks or even months at a time, participants in these studies wore goggles that altered the way the world around them looked. This included goggles that turn the incoming image upside down.

A person blinks while wearing an ‘invertoscope’ – goggles that turn the incoming image upside down. Dmitry Hoh/Wikimedia Commons, CC BY-SA

As you can imagine, people wearing these goggles at first found it really difficult to get by in their day-to-day activities. They would stumble and bump into things.

But this was temporary.

Participants reported seeing the world upside-down for the first few days, with difficulties navigating the environment, including trying to step over ceiling lights that appeared to them as on the floor.

Around the fifth day, however, performance seemed to improve. Things that were at first seen upside down now appeared the right way up, and this tended to improve with more time.

In other words, with continued exposure to the upside-down world, the brain adapted to the changed input.

More recent studies are beginning to identify which areas of the brain are involved in being able to adapt to changes in visual input, and what the limits of our ability to adapt might be.

Adaptation may even allow “colour blind” people to see colour better than is predicted from their condition.

Daniel Joyce, Senior Lecturer in Psychology, University of Southern Queensland