Immune system can hurt as well as help fight cancer

Researchers at the University of Pennsylvania School of Medicine have found that some proteins of the immune system can promote tumour growth. Investigators found that instead of fighting tumours, the protein C5a, which is produced during an immune response to a developing tumour, helps tumours build molecular shields against T-cell attack. These findings appeared online in Nature Immunology.

C5a is part of the complement system, one of the body’s immune defences against pathogens. When activated, the system’s proteins rid the body of microbes and foreign cells. Many cancer treatments are aimed at boosting the immune system to kill tumours.

 “Until now, everyone thought that the complement system was there to eliminate tumour cells. We found that in some conditions, the complement system can promote tumour growth, depending on the specific tumour and the specific environment in which the tumours are developing,” says John Lambris, PhD, the Dr Ralph and Sallie Weaver Professor of Research Medicine.

However, Penn researchers found that in a mouse model, activation of the complement system in tumour tissue leads to the generation of C5a, which recruits myeloid-derived suppressor cells (MDSC) to tumours. These MDSCs block the function of  CD8+ T cells, which would normally dismantle a tumour.

Researchers also found that blocking the C5a receptor on cell surfaces impairs tumour growth at the same rate of Paclitaxel, a chemotherapy drug. This discovery could lead to new cancer treatments with far fewer side effects than chemotherapy, surmise the investigators.

“Researchers are trying to introduce immune therapies and anti-tumour vaccines, but most of these vaccines fail,” says Lambris. “We show in this study a possible mechanism how to overcome this problem.”

Lambris and his team are conducting studies that apply the approaches outlined in this paper to five models of cancer.

(Source: Nature Immunology: Penn Medicine: October 2008)