tudy provides new information on immune system response to skin cancer treatment (Pic Credit: Skin Cancer Foundation)
Skin cancer patients may have a better prognosis if their T cells send messages of five specific genes in their immune response to drugs used to treat the disease, suggests a new study from the University of Birmingham.
Research on mice, cells in the laboratory and using publicly available data from patients with advanced melanoma before and after treatment with nivolumab is published in the journal Immunity.
T cells are white blood cells that protect the body from damage by viruses, bacteria and cancer cells and use their T cell receptor (TCR) to explore their environment to detect odors - called antigens - from germs. or bacteria.
that the TCR controls the behavior of diesel and can send messages to the T cell command center to elicit an immune response. This process is important for vaccine research and the treatment of autoimmune diseases, but particularly important for cancer treatments aimed at improving anti-tumor function of T cells.
The researchers conducted the study to better understand half of the antigen controls. How TCR messages are sent to the Command Center and how this affects the nature of the immune response. They wanted to investigate how Antigen controls the expression of so- called immune checkpoints, which act on immune responses like Barkes. It is these immune inhibitors like PD1 that drugs target that try to boost the immune response in cancer immunotherapy.
The lead author Dr. David Bending of the Department of Immunology and Immunotherapy at the University of Birmingham said: “ through our research, we discovered that the amount of antigen determined how many immune checkpoints are immune brakes T cell had on its cell surface”.
“ when we expose the cells to the highest amount of antigen, they stop sending signals to their command centre and this was because they had increase the number of immune brakes, Wish shut down the messengers. This made these T cell unable to respond to antigen agents for a period”.
By blocking one of the immune brakes, Kaul PD1, the researchers were able to see some of these unresponsive T cells awaken. They found that these awakened teachers not only started sending messages to their command centers, but the messages they sent were stronger and clearer.
“The response from the command centre was that the T Cells started to increase the number of messages from five specific genes,” added Dr Bending. “By looking for the messages from these five genes, we were able to show that these stronger and louder messages were increased in melanoma patients who survived for longer on drugs that block the immune brake PD1. We think that this means that those cancer patients whose immune cells can send messages from these five genes in response to drugs that target PD1, a good outcome is far more likely”.
The researchers said their results show that the immune system probably needs optimal levels of stimulation to produce the most effective immune response in skin cancer patients.
Dr Bending added: “Our research gives us an interesting insight into fundamental workings of the immune system. It suggests that both the amount of antigen around a T cell and also the number of immune brakes the T cells have at their surface are very important in controlling immune responses. Furthermore, we have shown that we can alter the balance of the immune response through stopping some of these immune brakes, which results in a stronger T cell response.”
The study provided a potential new benchmark for monitoring patients taking PD1 anticancer drugs. it may also be useful in exploring the potential of drug combinations targeting multiple immune checkpoints to try to further stimulate T cells in cancer patients.
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