Targeting the “don’t eat me” signal may improve immunotherapy for glioblastoma

“Don’t eat me!” That is how one might translate the signal that the cancer cells in a glioblastoma send to the macrophages (white blood cells specialized in removing dead and dying cellular matter) within the brain. Immunotherapy attempts to enable these cells to eradicate the abnormal cells, but to date, it has met with little success in terms of glioblastomas.

Researchers led by Professor Gregor Hutter from the Department of Biomedicine on the University and University Hospital Basel have recently used patient data, experiments with mice, and samples from human tumors to review considered one of these “don’t eat me!” signals and its inhibitory effect. Their findings, which can pave the best way for effective immunotherapies for glioblastomas, are actually being published in Science Translational Medicine.

The signal relies on sugar molecules called sialic acid glycans on the surface of the cancer cells. These sugar molecules are recognized by “receivers” on the surface of the brain’s macrophages and interpreted as “don’t eat me!” Hutter’s team of researchers reports that patients whose macrophages have especially high numbers of those “Siglec9” receivers have a lower survival rate.

Turning off the receiver

When the researchers used a genetic trick to remove the mouse variant of Siglec9 from the brain macrophages of laboratory mice, brain tumors in these mice grew significantly more slowly. One indicator that the macrophages were capable of partly hold the glioblastoma at bay: they now not had the receiver that allowed them to perceive the “don’t eat me!” signal, in order that they were capable of proceed with their task of removing the abnormal cells. The researchers also saw the identical effect after they implanted tumor cells that didn’t have any sugar molecules on their surface.

They confirmed this in experiments with surgically-removed brain tissue from glioblastoma patients, which the researchers cultivated within the lab. In the event that they gave the cultivated cells an antibody that blocked the Siglec9 receiver, they were capable of observe an activation of the immune cells within the tumor and the directly adjoining tissue.

Taken together, our results suggest that the sialic acid-Siglec axis may very well be a promising therapeutic goal.”

Professor Gregor Hutter, Department of Biomedicine, University of Basel

If the receivers on patients’ macrophages may very well be switched off with antibodies, existing immunotherapies might find a way to take full effect against glioblastomas as well. The following step within the team’s research is to look at in clinical studies whether it is feasible to offer an area dose of antibodies against the receiver within the brain and whether this has the specified effect.