Why cancer immunotherapies don’t work for everyone
Scientists have uncovered a mechanism by which cancer cells prevent the immune system from activating and attacking the cancerous invaders.
In a discovery that could improve treatments for autoimmune diseases and cancer, researchers have found a way to turn pro-inflammatory cells that boost the immune system into anti-inflammatory cells that suppress it, and vice versa.
When the immune system is imbalanced, either due to overly-active cells or cells that suppress its function, it causes a wide range of diseases, from psoriasis to cancer.
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By manipulating the function of certain immune cells, called T cells, researchers could help restore the system's balance and create new treatments to target these diseases.
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The new method to reprogramme specific T cells, revealed by scientists at Gladstone Institutes in San Francisco, is a step in that direction.
"Our findings could have a significant impact on the treatment of autoimmune diseases, as well as on stem cell and immuno-oncology therapies," said Gladstone Senior Investigator Sheng Ding, who is also a professor at the University of California, San Francisco.
The researchers studied two types of cells called effector T cells, which activate the immune system to defend our body against different pathogens, and regulatory T cells, which help control the immune system and prevent it from attacking healthy parts of its environment.
By drawing on their expertise in drug discovery, Ding's team identified a small-molecule drug that can successfully reprogramme effector T cells into regulatory T cells.
The study, published in the journal Nature, describes in detail a metabolic mechanism that helps convert one cell type into another.
This new approach to reprogram T cells could have several medical applications.
For instance, in autoimmune disease, effector T cells are overly activated and cause damage to body.
Converting these cells into regulatory T cells could help reduce the hyperactivity and return balance to the immune system, thus treating the root of the disease.
"Our work could also contribute to ongoing efforts in immuno-oncology and the treatment of cancer," explained Tao Xu, postdoctoral scholar in Ding's laboratory and first author of the study.
"This type of therapy doesn't target the cancer directly, but rather works on activating the immune system so it can recognise cancer cells and attack them," Xu added.
Many cancers take control of regulatory T cells to suppress the immune system, creating an environment where tumours can grow without being detected.
In such cases, the team's findings could be used to transform regulatory T cells into effector T cells to strengthen the immune system so it can better recognise and destroy cancer cells.
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