Australasian Science: Australia's authority on science since 1938

Triple-Agent Cells Fight Tumours

By Stephen Luntz

Immune cells that have been co-opted by tumours to assist their growth could be returned to a health-assisting role as a result of an Italian–Australian collaboration.

TIE2-expressing monocytes (TEMs) are cells that normally serve to create blood vessels and remodel tissue after damage. However, tumours co-opt them to generate the rapid growth of blood vessels they need to sustain their lethal growth. They are also used to help the tumour suppress the immune response that the body would otherwise use to fight it.

However, Dr Roberta Mazzieri of the University of Queensland’s Diamantina Institute recognised that the need for tumours to incorporate TEMs was a point of vulnerability. In combination with researchers at the Italy’s San Raffaele Scientific Institute she has removed stem cells from the bone marrow of mice and modified them to produce interferon-alpha.

Interferon-alpha returns to battle-readiness tumour-fighting immune cells whose natural instincts are suppressed by tumours. “The interferon-alpha protein has well-known anti-cancer properties, but previous efforts to use it as a cancer treatment have been limited because it has to be administered at high levels, which can be toxic,” says Mazzieri.

If the stem cells produced interferon-alpha in all the forms they transform into, the dose would be toxic. Mazzieri introduced an expression factor so that the interferon is only produced by those stem cells that convert into TEMs. “It was a lot of work to make them do that,” she says, but she has taken the process a step further. The modified TEMs produce interferon-alpha at all times, but production dramatically increases when a TEM is incorporated into a tumour.

“Tumours secrete a factor that tells cells to upregulate a specific gene. We used the promoter of that gene to increase interferon-alpha production,” says Mazzieri. “The effect is so potent you only need a few cells. You have one cell producing interferon-alpha and many cells responding.”

Mazzieri reported the success of her treatment for mice with breast cancer in Science Translational Medicine, and now hopes to demonstrate its applicability to humans. Breast cancer was chosen because “it is a common disease, and we also have a very good mouse model,” but the technique may be applicable to many forms of cancer.