Cancer treatment and immunity: another detail of the mosaic
Out of the fire and into the flames: how chemotherapy creates autoimmune inflammationKirill Stasevich, Compulenta
Antitumor medications give a signal to the synthesis of immune receptors, which regard the damaged DNA of tumor cells as a "signal to fight" and begin a "protective" inflammatory reaction.
Model of interaction of p53 (brown-blue-green) with DNA (red).
P53 is a transcription factor that triggers the synthesis of apoptosis and cell cycle proteins.
(Photo: Laguna Design.)
Flaws in DNA can provoke an immune response and an inflammatory response, according to researchers from the National Institutes of Health (USA). In their work, they found that damage to chromosomes stimulates the cell's production of so-called toll–like receptors, whose normal function is to recognize bacteria and other foreign agents.
Nevertheless, these receptors are able to bind to the legendary antitumor protein p53 (it is often called the "guardian of the genome"). The protein reacts to tumor degeneration and initiates the processes of apoptosis – "programmed suicide" in malignant cells, triggering the synthesis of mRNA (transcription) on the genes of "suicide" enzymes. Moreover, this interaction of immune receptors and p53 turned out to be characteristic only for primates.
The researchers worked with samples of human blood from which leukocytes were taken. The latter were treated with anticancer drugs to activate the synthesis of the p53 protein. As a result, along with p53, the cells also began to develop immune receptors, although with different activity in different blood samples. Moreover, the appearance of the receptors could be suppressed by the p53 protein inhibitor pythitrin. Obviously, p53, as in the case of apoptosis, is directly involved in the activation of receptor protein genes.
An article with the results of the study (The Toll-like receptor gene family is integrated into human DNA damage and p53 networks) is published on the PLoS Genetics website.
The immune response is always associated with the invasion of foreign agents into the body. Therefore, all the work may seem strange and incomprehensible biochemical tricks – if not for the fact of inflammation in many patients after chemotherapy. The explanation of such a reaction of the body to treatment may be as follows: most anti-cancer drugs "beat" the DNA of cancer cells. The destroyed DNA is perceived as a foreign agent and includes an immune response with all the inflammatory consequences. The difference in the level of immune receptor synthesis in different blood samples is thus explained by the individual sensitivity of the immune system to DNA damage.
Deciphering the mechanism of the relationship between tumor and immune processes will help not only to facilitate the treatment of cancer, but also to understand the nature and ways to combat autoimmune inflammation.
Prepared based on the materials of PhysOrg: Researchers find link between DNA damage and immune response
Portal "Eternal youth" http://vechnayamolodost.ru13.04.2011