A Tolerant Immune System May Increase Cancer Risk
For a malignant tumor to form, cancer cells must evade the immune system's attack. Numerous studies have already shown that cancer spreads particularly aggressively if there is an unfavorable balance between suppressing and active immune cells in the tumor microenvironment. “But we didn't know whether this is a consequence of an aggressive tumor, or rather, its cause,” said Rudolf Kaaks, PhD, an epidemiologist at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ). The research on this topic by Dr. Kaaks’ team is published by Barth et al in the Journal of the National Cancer Institute.
Study Findings
Dr. Kaaks and his team had a unique opportunity to pursue this question: The DKFZ is one of the study centers of the EPIC study, which investigates the links between diet and cancer in almost half a million people in the whole of Europe.
In the initial EPIC examinations from 1996 to 1998, blood samples were taken from all study participants and subsequently frozen. From the 25,000 participants in Heidelberg, the researchers now picked the blood samples from about 1,000 individuals who had developed cancer in the course of the observation period (lung cancer, colon cancer, breast cancer, and prostate cancer). Their control group consisted of 800 participants who were not affected by a malignancy.
Researchers counted the suppressing regulatory T cells in the blood samples and determined the ratio of these cells to the total number of T cells, which also comprises the tumor-fighting cells. This ratio is called “immunoCRIT”. As a rule, it holds true that the higher this value, the more the immune system is suppressed.
When comparing the cancer risk of EPIC participants with extremely high or extremely low immunoCRIT, the researchers found that if the value is strongly increased, lung cancer risk rises by 100%, and risk of colon cancer rises by approximately 60%. Women with very high immunoCRIT have a tripled increase in their risk of developing estrogen receptor–negative breast cancer. Here, however, the researchers think that for a definite statement, the case number might be too low. In cases of prostate cancer and estrogen receptor–positive breast cancer, the DKFZ epidemiologists found no links between immunoCRIT and cancer risk.
When tumor-fighting T cells are kept in check by inhibitory regulatory T cells, this is known as “peripheral immune tolerance.”
“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,” Dr. Kaaks said. “Hence, it is more likely to be the cause than the result of cancer.”
The investigators do not yet know why immune tolerance has an effect on certain cancer risks. A possible explanation may be that, according to prior research findings, tumors of the lung and bowel tend to be colonized by particularly high quantities of immune cells. They plan to extend their investigation to other types of tumors.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
