Washington, Mar 4 : Researchers at the University of Chicago Medical Center have found that targeting and killing the non-malignant cells that surround and support a cancer can cease tumour growth, paving the way for new treatments against cancers resistant to standard therapy.
The study, conducted on mice, was led by Hans Schreiber, MD, PhD, professor of pathology at the University of Chicago.
A great number of solid tumours have built elaborate mechanisms for avoiding recognition and elimination by the immune system. And because of their genetic instability they usually abandon the tumour antigen-presenting cell-surface structures that warn the immune system that these cells are harmful.
In the absence of these "flags," the white blood cells fail to identify and kill infected or cancerous cells. Then, these tumours often grow rapidly and do not respond to treatment with chemotherapy or efforts to boost the immune system's response to the tumour.
However, it is possible for the stroma, the layers of cells that surround a tumour, to gather tumour antigens and present them on their surface. These genetically stable surrounding cells retain the molecules that present tumour antigens, making them a good target for immunotherapy, and they often play an enabling role in tumour growth.
"We already knew that targeting the stroma is essential for eradicating established large tumours, because the stroma is like the 'root of the tumour. However, effects of current treatments that target stroma are usually transient and not cancer-specific. Since cancer is a genetic disease. We wondered whether mutant proteins are released into the surroundings and picked up by the stroma. If so, we can target the root of the cancer in a cancer-specific way to arrest or eradicate a tumour," said Schreiber.
For the study, the researchers injected T cells, the immune system's fighters, into mice with large established cancers.
It was discovered that these T cells, specifically engineered to recognize the tumour antigen, did not have any direct impact on the cancerous cells but still managed to kill stromal cells. This resulted in reduced tumour size and stopped the growth of tumours for more than 80 days.
However, targeting the stroma didn't eliminate all cancer cells, but it did stop or slow the growth of deep-rooted cancers after a single injection of T cells.
"Such growth arrest in patients would be an admirable achievement for many cancers and could also be used as an adjuvant to other therapies," wrote the authors.
The authors also indicate that tumour eradication is certainly preferable to tumour arrest.
"We can't target cancer cells when they have lost their antigen-presenting molecules," said one of the co-authors of the study.
He also said that one more concern was that other, healthy cells in tissues like the spleen could also pick up the antigens and become a target for T cells.
"We did not see this. Only tumour-derived stromal cells appear to pick up and present tumour antigen," he added.
The next step for the researchers is to test this approach for melanoma, breast and colon cancer. They are also studying this approach for human cancers. Early results suggest that "this approach might be useful for the human situation as well," said the authors.
The study is published in the latest issue of the journal Cancer Research.