O Immunotherapy is a promising strategy against cancer through the stimulation of the immunity system of the body and that destroys the tumor cells, but it only works in some cancers.
Now researchers at the Massachusetts Institute of Technology (MIT, for its acronym in English), in the United States, discovered in mice a new way to activate it to attack tumors, which they hope will allow this therapy to be used against more types of cancer. The study was published in the journal scientific signaling.
The researchers found that this treatment completely killed the tumors in nearly half of the rodents.
The new method consists of extracting tumor cells from the body, treating them with medications for chemotherapy and reconnect them to the tumor. When reintroduced, they act as a distress signal that stimulates the T cells. The researchers found that this treatment completely killed the tumors in nearly half of the rodents.
“Living cells with DNA damage, under certain conditions, are able to send a signal that wakes up the immune system,” he says. Michael Yaffe, one of the study’s authors and director of the MIT Center for Precision Cancer Medicine.
Activation of T cells
One class of drugs currently used for cancer immunotherapy are checkpoint blocking inhibitors, which unlocks T cells that are depleted and cannot attack tumors. These drugs have been successful in treating some types of cancer; however, there are many others against which they are not effective.
The authors set out to improve their performance by combining them with drugs for cytotoxic chemotherapy, in the hope that it would help stimulate the immune system to kill 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.
Immunotherapy is not effective in all tumors. The authors set out to improve its performance by combining it with cytotoxic chemotherapy drugs.
Currently, there are several clinical trials that combine chemotherapy and immunotherapeutic drugs, but so far little is known about the best way to combine these two types of treatment.
The MIT team started by treating the cancer cells with several different chemotherapy drugs, at different doses. Twenty-four hours after treatment, the researchers added dendritic cells to each plate and, after a further 24 hours, they introduced T cells into the same culture. Then they measured the ability of T cells to kill cancer cells.
Damaged but still alive cells
To their surprise, they found that most chemotherapy drugs didn’t help much, and those that did seemed to work better at low doses that didn’t kill many cells. Researchers later realized why: it wasn’t the dead tumor cells that stimulated the immune system, but the cells damaged by chemotherapy but still alive.
“This describes a new concept of immunogenic cell injury”, says the expert. “We showed that if the tumor cells were treated in a dish – when they were injected directly into the tumor again and the checkpoint inhibitors were administered – it was the living and the damaged cells that reactivated the immune system.”
The drugs that work best are those that damage the DNA of cancer cells but do not kill them
The drugs that work best are those that damage the DNA. According to the authors, when DNA is damaged in tumor cells, the cellular pathways that respond to stress are activated. These send distress signals that cause the T cells to spring into action and destroy not only the damaged cells but any nearby tumor cells as well.
“Our findings fit perfectly with the concept that danger signals within cells can communicate with the immune system, a pioneering theory. polly matzinger in the 1990s, although it is still not universally accepted,” explains Yaffe.
tumor removal
About melanoma and breast cancer, the researchers showed that this treatment completely eliminated tumors in 40% of rodents. Furthermore, when the researchers injected cancer cells into the same animals several months later, their T cells recognized them and destroyed them before they could form new tumors.
Scientists also tried injecting DNA-damaging drugs directly into tumors rather than treating cells outside the body, but found that this was not effective because chemotherapy drugs also damage T cells and other immune cells near the tumor.
When damaged cancer cells are re-injected several months after treatment, they are recognized and attacked by T cells.
Furthermore, introducing the damaged cells without checkpoint inhibitors had little effect. “You have to come up with something that can act as immunostimulant, but it is also necessary to release the pre-existing blockage in the cells of the immune system”, concludes the specialist.
Before testing this new treatment in patients whose tumors have failed to respond to immunotherapy, further studies will be needed to determine which drugs, and at what doses, would be most beneficial for different types of tumors, as well as to further analyze the exact details such as tumor cells damaged T cells stimulate such a strong T cell response.
Reference:
Sriram et al. “Injury response to DNA damage in living tumor cells promotes anti-tumor immunity.” Science Signaling. 2021.
Source: SYNC
Rights: Creative Commons.
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