Australian researchers uncover dual role for CD47 in glioblastoma, revealing protein drives tumour invasion beyond immune evasion

Australian scientists have identified a mechanism that drives the growth and spread of glioblastoma. The study, led by researchers at the Centre for Cancer Biology at the University of Adelaide, reveals a previously unknown role for a protein known as CD47 that has long been recognised for helping cancer cells evade the immune system. However, the new findings show it also plays a direct role in tumour development.

Glioblastoma is famously difficult to treat, with most patients surviving less than 18 months after diagnosis. Standard approaches such as surgery, radiotherapy and chemotherapy provide limited benefit and the disease often returns.

Protein found to drive tumour behaviour

The research demonstrates that CD47 actively supports tumour growth, movement and invasion into surrounding brain tissue.

Researchers found that CD47 is especially concentrated at the invasive edges of glioblastoma tumours, which are the areas responsible for spreading into healthy brain tissue.

“We’ve known for some time that CD47 acts as a kind of ‘don’t eat me’ signal that helps cancer cells hide from the immune system,” said Dr Nirmal Robinson, Senior Research Fellow at the University of Adelaide and a senior author of the study. “What we’ve discovered is that CD47 is doing much more than that; it’s actually driving the cancer’s ability to spread and grow.”

Researchers found that CD47 is especially concentrated at the invasive edges of glioblastoma tumours, which are the areas responsible for spreading into healthy brain tissue. Higher levels of the protein were also linked to significantly poorer survival outcomes in patients.

Blocking CD47 slows cancer progression

Working alongside Professor Stuart Pitson’s team, scientists used laboratory experiments and animal models to investigate the effects of removing or blocking CD47. They found this approach significantly reduced tumour cell proliferation, migration and invasion.

In some cases, tumours lacking CD47 grew more slowly and survival time in models nearly doubled. Notably, these effects occurred even without the presence of immune cells, confirming that CD47’s tumour-promoting role extends beyond immune evasion.

Key molecular pathway uncovered

The team also identified a partner protein, ROBO2, which operates downstream of CD47 and contributes to tumour growth and spread. Further investigation revealed that CD47 protects ROBO2 from being broken down inside the cell.

The team also identified a partner protein, ROBO2, which operates downstream of CD47 and contributes to tumour growth and spread.

This protection occurs because CD47 sequesters another protein, ITCH, which would otherwise mark ROBO2 for destruction.

“Essentially CD47 is shielding ROBO2, allowing it to accumulate and drive tumour progression,” said Dr Ruhi Polara, Research Associate at the University of Adelaide who also led the research alongside Dr Robinson. “When we remove CD47, ROBO2 is degraded and the cancer cells lose their ability to grow and invade effectively.”

New directions for treatment

The discovery of the CD47-ITCH-ROBO2 pathway provides a new understanding of how glioblastoma behaves and opens up potential avenues for treatment. Although therapies targeting CD47 are already being trialled in other cancers, they have shown limited success in glioblastoma.

The researchers suggest that directly targeting this newly identified pathway, or interfering with the stabilisation of ROBO2, may be more effective.

“By understanding this mechanism we now have new targets to explore,” Dr Polara said. “This could lead to the development of therapies that specifically block the tumour’s ability to spread, which is one of the biggest challenges in treating glioblastoma.” 

Rethinking cancer biology

The findings also highlight the importance of looking beyond immune system interactions when developing cancer therapies.

This work changes how we think about CD47.

“This work changes how we think about CD47,” said Dr Robinson. “It’s not just an immune checkpoint; it’s a central regulator of tumour biology in its own right.”

Researchers say further work is needed to translate these findings into clinical treatments but the study is an important step in potentially combatting one of the most devastating forms of cancer.