Immune system changes make recurrent tumours more aggressive

Washington: The enhanced aggressiveness of recurrent tumours may be due to changes in the body`s immune response, scientists led by an Indian-origin researcher have claimed.

The traditional view of recurrent tumours is that they are resistant to therapy because they`ve acquired additional genetic mutations that make them more aggressive and impervious to drugs.

Now, researchers at the Perelman School of Medicine at the University of Pennsylvania found in an animal model that the increased aggression of recurrent tumours could be due to changes in the body`s immune response.

"Typically when a patient has a tumour recurrence, their oncologist treats them, much like they treated them for the primary tumour - with drugs aimed at the tumour cells themselves," said senior study author Sunil Singhal, assistant professor of Surgery and director, Thoracic Surgery Research Laboratory at the Perelman School of Medicine.

"But we`ve found that it might be better to attack the tumour cells and knock down the bad immune cells that are protecting the tumour," Singhal said.
To assess the impact of anti-cancer vaccines on primary and recurrent tumours, the researchers immunised mice that had a primary or a recurrent tumour in their flank.

Although both groups of animals developed an immune response to the vaccine, only the primary-tumour animals showed tumour shrinkage in response to the vaccine. The recurrent tumours appeared unaffected by the vaccine response.

Despite the prevailing models of tumour recurrence - which emphasise genetic changes in the tumour cells themselves - Singhal and colleagues could not find substantial genetic or behaviour differences in the recurrent versus primary tumours that might account for the pattern of response.

By contrast, when they looked at the types of immune cells in and around the tumour, Singhal`s team saw a big difference. The recurrent-tumour mice had a large increase in the number of regulatory T cells, compared with primary-tumour animals.

That could be important, said Singhal, because T regulatory cells are responsible for holding other immune cells in check and blocking immune responses.

Additionally, macrophages that protect the tumour cells from immune system also increased in number and activity in the recurrent-tumour animals.

Remarkably, when the researchers treated recurrent-tumour animals with drugs that block macrophage activity, tumour growth slowed significantly.

However, the same drugs had no effect on primary-tumour animals.
Singhal said it is not clear exactly what triggers the immune system changes, but whatever it is appears to happen at the time of surgery. His group has already started looking for alterations in signalling molecules.

The study was published in the Proceedings of the National Academy of Sciences.