Tumours arise when cells shake off their restraints and start to multiply out of control.

But how fast a tumour grows does not depend solely on how quickly the cancer cells can divide, a new study has found.

By examining brain tumours in mice, researchers at Washington University School of Medicine in St. Louis discovered that immune cells that should be defending the body against disease sometimes can be enticed into providing aid and comfort to tumour cells instead.

The more immune cells a tumour can recruit to its side, the faster the tumour grows, the researchers found.

The findings, published May 29 in the journal Neuro-Oncology, suggest that targeting immune system cells could potentially slow brain tumour growth in people with the genetic condition neurofibromatosis type 1 (NF1).

"It's not just all about the tumour cell anymore," said senior author David H. Gutmann, MD, PhD, the Donald O. Schnuck Family Professor of Neurology and director of the Washington University Neurofibromatosis Center.

"It's also about what happens in the tumour environment that drives brain cancer growth. This gives us another way to attack these tumours beyond merely killing the cancer cells - namely, interrupting the communication between tumour cells and immune system cells."

While people with NF1 usually come to medical attention for birthmarks on their skin, they are also at increased risk of developing tumours.

One of the most common of these tumours in children is a low-grade brain tumour called an optic glioma, which affects the optic nerve that connects the brain and the eye. Some of these tumours can cause vision loss.

Unfortunately, NF1 is a notoriously variable disease.

Doctors can't predict what kinds of tumours a person will develop, how fast these tumours will grow, or what types of medical problems the tumours will cause - all of which make it difficult for doctors to decide when a tumour needs to be treated with chemotherapy and when it is safe to simply watch and wait.

To better understand why some tumours grow faster than others, first author Xiaofan Guo, MD, a graduate student in Gutmann's research laboratory, created five mouse strains with different genetic changes in the NF1 gene and elsewhere in the mouse's genome.

The five strains varied widely in tumour development and growth.

Mice belonging to three of the strains grew tumours starting at about 3 months of age, with the tumours in one strain of mice growing particularly fast.

Members of the fourth strain didn't grow tumours until they were about 6 months old, and only a quarter of mice in the fifth strain developed brain tumours on the optic nerve at all.

When the researchers isolated tumour cells from the mice and grew them in a dish, they found little difference in tumour cell growth.

The growth rates and other properties of the cancer cells were very similar, no matter which mutation the tumour cells carried.

What did correlate with overall tumour proliferation in mice was the presence of two kinds of immune cells - microglia and T cells - within the tumours.

Guo and former postdoctoral research fellow Yuan Pan, PhD, discovered that the tumour cells themselves were releasing immune system proteins that attracted immune cells to the tumour.

"Cells that should be part of the brain's defence against tumours have become part of the process of making and growing a tumour," said Gutmann, who is also a professor of genetics, of neurological surgery and of paediatrics.

The researchers now are trying to take advantage of this relationship between tumour cells and immune system cells to find new ways to treat brain tumours in people with NF1.

One strategy is to slow tumour growth by preventing microglia or T cells from providing support to the cancer cells. However, a more ambitious strategy is to reprogram the T cells to no longer aid tumour cell growth.

"The idea is to use T cells as Trojan horses," Gutmann said.

"These are experiments currently ongoing: We're trying to change the T cells so that when they enter the brain, instead of promoting the tumour, they shut it down."

Source: Washington University School of Medicine in St. Louis