Breakthrough could lead to effective cancer vaccines

Posted by Emma Woollacott

Scientists researching cancer vaccines have made a significant breakthrough that could allow many cancers, including breast and colorectal cancers, to be targeted.

A team at the University of Cambridge says it's discovered one of the reasons why many previous attempts to create vaccines have failed.

Vaccines designed to trigger the immune system into attacking cancerous cells in tumours have been shown to trigger an immune response in the body. Unfortunately - and inexplicably - though, they've almost never affected the growth of tumors. 

Immunologists suspected that the activity of immune cells was somehow suppressed within the tumor, but were unable to work out why.

Published in Science, the Cambridge report focuses on a type of stromal cell found in many cancers which expresses fibroblast activation protein alpha (FAP). These cells play a major role in suppressing the immune response in cancerous tumors, thereby rendering vaccines ineffective. 

And the team found that destroying these cells prevented the immune suppression response, allowing the immune system to start controlling the tumor.

"Finding the specific cells within the complex mixture of the cancer stroma that prevents immune killing is an important step," says Douglas Fearon of the Department of Medicine. "Further studying how these cells exert their effects may contribute to improved immunological therapies by allowing us to remove a barrier that the cancer has constructed."

Fearon and his team studied a type of cell that expresses a unique protein often associated with wound healing - fibroblast activation protein alpha (FAP).  FAP-expressing cells are found in many cancers, including breast and colorectal cancers.

To fond out whether FAP-expressing stromal cells contribute to the resistance of a tumor to vaccination, they created a transgenic mouse model which allowed them to destroy the cells. 

When this was done in tumors in mice with established Lewis lung carcinomas, the cancer quickly began to die - even though only two percent of the cells in this type of tumor are FAP-expressing.

"These studies are in the mouse, and although there is much overlap between the mouse and human immune systems, we will not know the relevance of these findings in humans until we are able to interrupt the function of the tumor stromal cells expressing FAP in patients with cancer," warns professor Fearon.

"It should be noted, however, that the FAP-expressing stromal cell was actually first found in human cancer by Lloyd Old and his colleagues 20 years ago."