Researchers from the University and University Hospital Basel, Switzerland, have identified a new strategy to fight glioblastoma multiforme (glioblastoma), an aggressive brain tumour. Their findings, published in the journal Science Translational Medicine on 19 July, could pave the way for enhancing immune responses against these tumours.
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Stealthy glioblastomas
The brain has its own macrophages, immune cells that engulf and destroy malignant cells. However, in the case of glioblastoma and some other tumours, the cancer cells have a strategy to evade the immune cells: they send ‘don’t eat me’ chemical signals.
Previous studies have found that specific sugar molecules on the surface of the cancer cells send these signals.
Professor Gregor Hutter, the lead author of the current study, explains that these sugar molecules tell the receiver molecules on immune cells not to attack the tumour.
“This basically shuts the main function of the phagocytes [macrophages], to fight against the tumour and in consequence also leads to a suppressed T-cell response [of the immune system],” he tells Happiest Health.
Thus, these cancer cells evade the immune system’s natural defences, allowing them to grow and multiply indefinitely. While scientists were aware of this mechanism, previous attempts to overcome it had not succeeded.
Cracking the glioblastoma code
In the present study, Professor Hutter and the team blocked the immune system checkpoint that picks the ‘don’t eat me’ signals, focused on gene SIGLEC9.
Previous studies had shown that the SIGLEC9 gene in the macrophages of the brain’s immune system acts like an inspector at the checkpoint, picks up the ‘don’t eat me’ signals from cancer cells and stops attacking them.
In experiments on mice with glioblastoma, the researchers used a genetic technique to remove the SIGLEC9 gene from macrophages, following which tumour growth reduced significantly in a few weeks. They also saw that the macrophages functioned normally and effectively, clearing the tumour cells.
To reduce the growth of the cancer cells, the researchers also suppressed the sugar molecules present in the tumour cells. They implanted lab-modified tumour cells without the sugar molecule in the mice. This dual strategy further enhanced the immune response to the tumour, thereby reducing it.
The eureka moment!
Further, the researchers performed experiments on cancerous brain tissue samples from people with glioblastoma. They cultivated the cells in the lab and treated them with an antibody that blocked SIGLEC9 .
Here, too, they observed a similar immune response in the tumour and surrounding tissue. “The only way to treatment success is combinations of innate and adaptive checkpoint inhibition and something that also targets the tumour cells in my view,” says Prof Hutter.
Although therapies targeting the immune system (immunotherapy) have shown limited success in treating glioblastomas in the past,Professor Hutter is optimistic about the potential of their dual approach. “It is certainly promising, but ultimately, we need clinical trials to compare this treatment to the standard of care,” he concludes.
