The researchers found that an unfavorable ratio of immune cells is more likely to be the cause than the result of cancer.
A paper on the study, by researchers from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg, is published in the Journal of the National Cancer Institute.
Malignant tumors develop when cancer cells - which arise from time to time and usually get mopped up - manage to escape the clutches of the immune system.
Previous studies have also suggested that cancer spreads more aggressively when the balance between antitumor and tumor tolerance in the immune system favors the latter in the microenvironment surrounding cancer cells. Scientists use the term "peripheral immune tolerance" to describe what happens when tumor-fighting T cells are kept in check by inhibitory regulatory T cells.
"But we didn't know whether this is a consequence of an aggressive tumor or rather its cause," notes Dr. Rudolf Kaaks, DKFZ epidemiologist and coauthor of the new study.
The data for the study came from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.
For the last 15 years, EPIC has been following half a million participants recruited across 10 European countries to investigate the links between diet and cancer. The DKFZ in Heidelberg is one of the study centers and is following 25,000 participants. Blood samples - taken when the participants joined the study in 1996-1998 and periodically since - are kept in frozen storage.
For their research, Dr. Kaaks and colleagues examined the blood samples of around 1,000 individuals who developed cancer over the period of the follow up since enrollment. The cancers they chose to focus on were lung cancer, colon cancer, breast cancer and prostate cancer.
They also selected a control group of around 800 individuals who did not develop cancer and examined their blood samples for comparison.
Researchers calculated a measure of immune tolerance to cancer
The researchers calculated a measure of immune tolerance to cancer that they called "immunoCRIT." This is a ratio of the number of immune T cells that suppress the immune response to cancer (inhibitory regulatory T cells) to the total number of immune T cells (including the tumor-fighting T cells).
For each of the blood samples, they calculated the value of immunoCRIT. The idea is that the higher the value of immunoCRIT, the more the immune system tolerates tumor growth.
The team then explored how immunoCRIT varied among the participants over the observation period and how this correlated with any cancer development.
They found that if the value of immunoCRIT increased strongly over the follow-up in participants who had extremely high or extremely low immunoCRIT at the start, then their risk of developing lung cancer rose by 100%, and their risk of developing colon cancer rose by around 60%.
They also noticed that women with very high immunoCRIT had a triple increased risk of developing estrogen-receptor negative (ER-negative) breast cancer - but they remark they are not too confident about this finding because of the small number of cases.
They found no significant links between immunoCRIT and cancer risk for prostate cancer and estrogen-receptor positive (ER-positive) breast cancer.
Dr. Kaaks concludes:
"With this study, we have demonstrated for the first time that the unfavorable ratio of immune cells already prevailed long before the onset of the disease. Hence it is more likely to be the cause than the result of cancer."
The team does not know why immune tolerance appears only to affect the risk of certain types of cancer. Previous research shows high levels of immune cells tend to accumulate in tumors of the lung and the bowel - perhaps this is one reason. They now plan to use immunoCRIT to investigate other types of cancer.
Meanwhile, Medical News Today recently reported a study that suggests targeting PAT4, a protein that helps cancer cells source nutrients, could stop tumors growing. The researchers found that aggressive cancer cells produce more PAT4, allowing them to better use available nutrients than the cells around them.