Aging of the immune system and cancer
Scientists are changing their view on the causes of cancer
Yulia Bondar, Copper News, based on EurekAlert: Aging immune system may explain age-related cancer risk increase
Researchers from the University of Dundee (University of Dundee, Scotland) are ready to reconsider the generally accepted views on the causes of cancer. The study showed that the leading cause may not be mutations, which are currently the focus of most searches for anti-cancer drugs, but the aging of the immune system.
A drawing from an article by Palmer et al. Thymic involvement and rising disease incident with age (PNAS, 2018) – VM.
For decades, it has been believed that mutations that arise either as a result of hereditary predisposition, or as a consequence of lifestyle and environmental factors, usually become the main cause of tumor development. And the fact that the increase in the incidence of cancer is observed with age, from the traditional point of view, is explained by the number of accumulated mutations.
A team of scientists from the University of Dundee, together with scientists from Heriot-Watt University, the University of Edinburgh and the Curie Institute (Institut Curie, France), showed that a decrease in the function of the immune system with age may actually be a more compelling reason for an increase in cancer incidence than multiple mutations.
Following the hypothesis that an aging immune system can lead to an increase in the incidence of cancer in the same way as the susceptibility to other diseases increases with age, the scientists examined data on 2 million cases of cancer in patients aged 18-70 years. They then developed a mathematical equation for the estimated increase in cancer incidence due to the decreasing function of the immune system and compared it with age profiles for 100 different types of cancer.
It turned out that the formula obtained by scientists modeled the data on the incidence of cancer much more accurately than the hypothesis of multiple mutations. For example, the function of the immune system usually decreases more slowly in women than in men, and the resulting formula more accurately corresponds to gender differences that cannot be explained by the theory of accumulation of mutations.
This suggests that the immune system, especially when its functions are reduced, may play a much greater role in the development of cancer than previously thought. If this version is confirmed by further research, it could have serious implications for cancer prevention and treatment approaches around the world.
"Almost all major cancer research is based on how we can find the right mutations, target them and thereby cure the disease. We do not deny the fact that mutations cause cancer, but we ask the question: can only mutations explain the rapid increase in cancer incidence with age, when aging causes other profound changes in the body," explained Dr. Thea Newman, professor of biophysics and systems biology at the University of Dundee.
The main cause of aging of the immune system is a decrease in the function of the thymus gland. It is here that T cells are produced, which circulate in the body, killing dysfunctional cells or foreign agents. The decrease in the functioning of the thymus begins at about the same age in all people. Then, every 16 years, the size of the thymus decreases by about half, which causes a drop in T-cell production. Scientists have found a strong correlation between an increase in the chances of developing certain types of cancer and a drop in new T-cell populations.
"The hypothesis of immunological observation is that cancer cells constantly arise in the body, but usually the immune system kills them before a new tumor can form and begin to grow. T cells are constantly looking for cancer cells and destroying them. If they can't find them fast enough or the immune system is too weak, then the cancer has a chance to start growing. These chances will increase with age, as the thymus decreases all the time and the number of T cells decreases," said Dr. Sam Palmer.
"For our model, we presented a war between T cells and cancer cells, which cancer cells win as soon as their number exceeds a certain threshold. Then we set this threshold in accordance with the age proportional to the drop in T-cell production. This simple hypothesis explains most of the data on cancer incidence," he added.
"The increase in the incidence of cancer with age is slower in women, although we naively expected that it would be effectively gender-neutral. However, the thymus gland in women decreases more slowly in size, so we were able to predict the differentiated incidence of cancer depending on gender, which once again shows that our model is more accurate than the traditional model of genetic mutations," said Dr. Luca Albergante.
A group of scientists tested their model according to the National Cancer Surveillance Program (SEER) in the USA. The test results showed that many cancers seem to be really strongly associated with the decline of the immune system, while others are most likely associated with a combination of a decrease in the immune system and multiple mutations.
"We believe that our results are extremely important and show the need to take the immune system even more seriously in cancer research. We need to focus on how the function of the thymus can be controlled – perhaps through transplantation or controlled regeneration we can increase the number of T cells produced by the thymus," concluded Professor Clare Blackburn from the University of Edinburgh.
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