Researchers at the Mainz University Medical Center have discovered a new signal pathway employed by skin cancer cells to avoid attack by the immune system. In an animal model and through analysis of human tissue samples, Dr. Toszka Bohn, Dr. Steffen Rapp and Professor Tobias Bopp were able to demonstrate the significant role played by a specific protein called ICER. Tumors grow less rapidly when ICER is not present. The researchers recently presented their study in Nature Immunology.
Over the course of evolution, the immune system has developed effective mechanisms to detect pathogens invading the body from outside and to eliminate them before they can cause major damage canadianpharmtabs.com. However, the body is also exposed to dangers from inside. Such threats can take the form of genetic mutations from which a tumor can ultimately develop. But how do these abnormal cells elude detection by the immune system? Which immune evasion mechanisms do they use? In order to be able to develop new immunotherapy approaches in the treatment of cancer, it is first necessary to identify these mechanisms.
“In our paper in Nature Immunology, we report on a previously unknown immunoevasion mechanism used by the type of skin cancer known as melanoma,” said Dr. Toszka Bohn, researcher at the Institute for Immunology of the Mainz University Medical Center.
Among other things, cancer cells are characterized by very rapid growth. The cells of tumors need a great deal of energy for this, which they obtain by means of a high rate of metabolic turnover. “We were able to show that the rate of metabolic turnover in melanomas is particularly high, which results in an abnormal acidification of the tumor environment,” explained Professor Tobias Bopp, co-author and spokesperson of the Research Center for Immunotherapy (FZI). Because of this acidic micromilieu, certain immune cells called macrophages that have migrated into the tumor develop into M2 macrophages, which are a specific sub-type of anti-inflammatory macrophage.
M2 macrophages are usually involved in wound healing processes and the regeneration of damaged tissue. These properties now benefit the growth of the tumor. Through a more detailed analysis of the mechanism, the researchers discovered that a protein known as inducible cAMP early repressor (ICER) is substantially involved in the process of macrophage transformation into the M2 sub-type.
“In an animal model we were further able to prove that the immune response to tumors is boosted or, in other words, the growth of cancer is slowed, if we eliminate ICER or interrupt the corresponding signal pathway,” Dr. Toszka Bohn pointed out. “Comparable results obtained in analogous experiments using human tissue as samples underline the clinical relevance of our findings.”
Source: Read Full Article