Author:Tan Suojun
T cell dysfunction contributes to tumor immune escape in cancer patients and is particularly severe in glioblastoma (GBM). Recently, researchers at the Duke Cancer Institute have discovered traces of missing T cells in GBM patients, which are largely isolated in the bone marrow. Isolation of T cells in the bone marrow is a tumor-adapted pattern of T cell dysfunction, and its reversal may be a promising aid for immunotherapy.
GBM can have an unusual effect on the body's immune system, often leading to a sharp decline in the number of circulating T cells that help strengthen the body's defenses. Although more and more people use immunotherapy to stimulate the body's natural ability to resist invasive tumors, the fate of T cells remains unclear.
Now, researchers at the Duke Cancer Institute track down missing T cells in patients with glioblastoma – they find a lot of glial cells in the bone marrow. The study, published in the August 13 issue of Nature Medicine, opened up a new area of exploration for adjuvant treatment of cancer.
"The problem with all these immunotherapies is that the immune system has been hit, especially for glioblastoma and other tumors that spread to the brain," said lead author of the article, Peter E, director of neurosurgical brain tumor immunotherapy programs at Duke University. Dr. Fecci said, "If the goal is to activate T cells, but T cells do not exist, then the treatment effect can not be said."
Fecci led the team to look for missing T cells after observing that many of the newly diagnosed glioblastoma patients had the same immune system as the immune system of AIDS patients.
Most normal people have CD-4 "helper" T cells, counted between 700 and 1000, and many untreated glioblastoma patients have a count of 200 or less, indicating that their immune function is very high. Poor, susceptible to various infections, and even lead to cancer deterioration.
Image source: Alisa Weigandt /Duke Health
Researchers at the Duke Cancer Institute tracked missing T cells in patients with glioblastoma in the bone marrow.
Initially, the researchers looked for missing T cells in the spleen, because under certain conditions, the spleen hides T cells. But the spleen is abnormally small, and the thymus is also a potential T-cell sanctuary. They then decided to examine the bone marrow and found clusters of T cells there.
Fecci said: "This is very strange, this phenomenon can not be seen under any disease state. The brain can regulate the mechanism of T cell entry, but it is being replaced by tumors, thus limiting the ability of the immune system to attack tumors."
When examining hidden T cells, Fecci and colleagues found that there is a lack of a receptor called S1P1 on the surface of T cells, which is the key "key" for T cells to leave the bone marrow and lymphatic system. Without the "key", T cells are locked in, unable to spread and fight infection, let alone cancer.
To clarify how the brain triggers this S1P1 receptor dysfunction, the research team did further research. The current theory is that the S1P1 receptor receives a signal in some way that retracts from the cell surface back into the cell.
"Interestingly, when we recovered T cell receptors in mice, T cells left the bone marrow and entered the tumor, so we know the process is reversible," Fecci said excitedly.
Fecci's team is working with Duke University scientist Robert Lefkowitz (received the Nobel Prize in Chemistry for the S1P1 receptor category) to develop molecules that restore cell surface receptors.
Fecci said: "We hope this discovery can provide a new way to calm down autoimmune disorders by activating T cell sequestration, allowing more people to benefit from immunotherapy."
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