Leigh Engineering Faculty Boulevard, Tel Aviv University. Photo: Ido Perelmutter via Wikimedia Commons.

Israeli researchers have discovered a “double agent” mechanism of immune system cells that may help improve the therapy for one of the most common and deadly types of brain cancer.

In a first, scientists at the Tel Aviv University examined the development of a glioblastoma cancerous tumor in animal models with a functioning immune system, to simulate the development of the tumor in humans and monitor the interaction between the immune system and cancer cells. Previous research to examine the development of malignant tumor in animal models was only carried out without an active immune system, according to the scientists.

The study revealed that certain immune system cells, also known as neutrophils, act as “double agents” — in their primary function they attack and kill cancer cells, but over time it was found that they “change sides” and begin to support and intensify the aggressiveness and developmental threat of the tumor.

“Neutrophils are the front-line soldiers of the immune system,” said Dr. Dinorah Friedmann-Morvinski, who led the study at the George S. Wise Faculty of Life Sciences and Sagol School of Neuroscience at Tel Aviv University. “We learned that the neutrophils actually change their role. They are mobilized by the tumor itself, and from being anti-cancerous, become pro-cancerous; as a result, they aggravate the damage that the tumor itself creates.”

Glioblastoma accounts for the majority of brain tumors and is highly aggressive, known as one of the most lethal cancers in humans. The average survival time of patients with glioblastoma is 12 to 15 months from the time of diagnosis. Glioblastoma spreads fast and unpredictably, making it challenging to treat with existing approaches, including surgery, radiation therapy, chemotherapy or certain targeted therapies.

“Unresponsiveness may result, at least in part, because these therapies only aim to target cancer cells and neglect the complex microenvironment around tumors that undergo drastic changes during disease development,” according to the study published in the Cell Reports journal.

The researchers found that neutrophils play an important role in interacting with cancerous growth. The immune system cells originate in the bone marrow and their purpose is to “swallow” or kill bacteria and fungi and fight infections caused by them.

“The study showed that the change in the properties of neutrophils takes place in the bone marrow itself — where there is no tumor at all: the cancerous tumor is located only in the brain, and from there it succeeds in changing the properties of the cells it recruits,” added Dr. Friedmann-Morvinski. “The new findings of this study may also shed light on immunotherapeutic therapies, which have been gaining a lot of momentum in recent years. In one type of immunotherapy treatment, T cells are removed from the patient’s body, processed, and returned to the body with increased healing abilities.”

“One of the major problems today is that these cells that have been sent to heal are suppressed and their actions stifled,” she said. “If we know how to change the interaction between neutrophils and T cells so that they are not suppressed, this will have implications for the effectiveness of immunotherapy.”