SCIENTIFIC EDUCATIONAL CENTER science idea

Researchers at the Massachusetts Institute of Technology have discovered a new way to get the immune system to attack a patient's tumors. To do this, they remove tumor cells from the body, expose them to chemotherapy drugs, and then return them back to the tumor. After that, the patient's own T cells are activated, which begin to destroy the tumor.
Immunotherapy is a promising cancer treatment strategy by stimulating the body's own immune system to destroy tumor cells. Unfortunately, it only works for certain types of cancer at the moment. One type of drug used in cancer immunotherapy is checkpoint inhibitors, which stimulate an immune response against a tumor. Immune checkpoint inhibitors are specific molecules secreted by tumors to defend against the immune system. By inhibiting them, that is, stopping their action, scientists activate the body's defenses. Checkpoint inhibitors have been shown to be successful in treating some cancers, but are not effective against many others.
Led by Professor Michael Yaffe and Professor Darrell Irvine, MIT scientists decided to try to improve the effect of checkpoint inhibitors by combining them with cytotoxic chemotherapy drugs, in the hope that chemotherapy would help stimulate the immune system to destroy tumor cells. This approach is based on a phenomenon known as immunogenic cell death, in which dead or dying tumor cells send signals that attract the attention of the immune system.
Scientists began by treating cancer cells with several different chemotherapy drugs at varying doses. After 24 hours of treatment, the researchers added dendritic cells (a special type of white blood cell) to the culture, followed by T cells 24 hours later, and then measured how well the T cells were able to kill cancer cells. To their surprise, the scientists found that most chemotherapy drugs did not help much. The ones that actually worked turned out to be best at low doses that did not kill many tumor cells. Later, the researchers realized why this is so: the immune system was stimulated not by dead tumor cells, but by cells that were damaged by chemotherapy, but remained alive. “When you create cells that have DNA damage but do not die, under certain conditions, these living damaged cells can send a signal that activates the immune system,” says Professor Michael Yaffe.
The drugs that appear to be most effective with this approach are those that cause DNA damage. The researchers found that when DNA damage occurs in tumor cells, they activate cellular pathways that respond to stress. These pathways send chemical distress signals that trigger the T cells to activate and destroy not only those damaged cells, but any tumor cells in the vicinity.
“Our results fit perfectly with the concept that distress signals within cells can interact with the immune system. This theory was first proposed by Polly Matzinger of the National Institutes of Health in the 1990s, although it has not yet gained widespread acceptance, ”says Professor Jaffe.
In experiments on mice with melanoma and breast tumors, the new method completely eliminated tumors in 40% of mice. What's more, when researchers injected cancer cells into the same mice a few months later, their T cells recognized them and destroyed them before they could form new tumors. The researchers also tried to inject DNA-damaging drugs directly into tumors instead of targeting cells outside the body, but they found that this proved ineffective because the chemotherapy drugs also damaged T cells and other immune cells near the tumor. In addition, administration of damaged cells without checkpoint inhibitors had little effect.
Professor Jaffe hopes to test this approach in patients whose tumors do not respond to immunotherapy.
Article published in Science Signaling
PHOTO: T-lymphocyte © Blausen Medical
Source: Maxim Russo polit.ru, sci-dig.ru