These steroids boycott some cancer treatments

2023-06-23 17:01:18

Immunotherapy is one of the newest and most powerful weapons against cancer. It prompts the immune system to recognize tumors as intruders in the body and attack them. But not all patients respond well to immunotherapy. Because? Scientists are not always sure.

Sometimes patients treated with immunotherapy experience side effects that a type of steroid, called glucocorticoids, can treat. Glucocorticoids are often used to regulate the immune response in conditions such as asthma, Crohn’s disease and even Covid-19. However, it is also unknown how they work. However, its operation is also a mystery.

Now, researchers from Cold Spring Harbor Laboratory (USA) may be closer to answering both questions. His new research indicates that glucocorticoids may indirectly cause the failure of some immunotherapy treatments by boosting the production of a protein called cystatin C (CyC). Higher CyC levels are related to poorer results from this type of therapy.

The researcher Tobias Janowitz affirms that «theGlucocorticoids are very potent suppressors of immunity and are therefore used to treat autoimmunity.», which is when the immune system attacks healthy cells. “We had previously shown that glucocorticoids can also interrupt cancer immunotherapy. Now, here we have perhaps a clue as to how they do it.

Janowitz’s lab studies the whole-body response to cancer. For this study, a huge set of genetic data from the UK Biobank of nearly 500,000 volunteers, including cancer patients.

The scientists found that patients more likely to produce CyC in response to glucocorticoids had a worse overall survival rate. These patients were also less likely to benefit from treatment. This suggests that CyC production within a tumor may contribute to the failure of cancer immunotherapy.

To confirm CyC’s relationship with cancer, the researchers turned to traditional laboratory work. In mice, deleted a CyC-producing gene so that it would no longer be present in cancer cells. They found that tumors without CyC grew more slowly.

“It’s really powerful to approach this from multiple angles and support the findings through many approaches,” he explains. «Smart genetic models gave us some pointers on which experiments to design to help us answer the question of what this molecule does.a».

“The research has given me an impetus to find out more about the function of this molecule, specifically in the context of cancer immunotherapy,” he says. “Perhaps their role can be targeted to improve the success of cancer immunotherapy,” he adds.

The research is published in Cell Genomics.