Steroids could be the cause of immunotherapy failure in some patients

The immunotherapyone of the most powerful tools against cancerprompts the immune system to recognize tumors and attack them but these treatments do not always work. Today, a study suggests that some drugs in these therapies could be the cause.

The study, led by researchers from the Cold Spring Harbor Laboratory (CSHL) in the United States, has been published this Friday in Cell Genomics.

Sometimes immunotherapy patients experience side effects that steroids called glucocorticoids (GCs) can treat.

GCs are used to regulate the immune response in conditions such as asthma, Crohn’s disease, and even COVID-19, but how they work is not well known. Its operation is a mystery.

The new study reveals that GCs can indirectly cause the failure of some immunotherapy treatments by boosting the production of a protein called cystatin C (CyC), whose high levels are associated with worse results from this type of therapy.

“GCs are very potent suppressors of immunity and are therefore used to treat autoimmunity,” which is when the immune system attacks healthy cells, explains Tobias Janowitz, a professor at CSHL.

“We had previously shown that GCs can also interrupt cancer immunotherapy. Now, here we have perhaps a clue as to how they do it.”underline.

The body’s response

Janowitz’s lab investigates the body’s response to cancer, and for this study, he and his lab’s doctoral student, Sam Kleeman, teamed up with Hannah Meyer, an expert in quantitative biology.

Together they analyzed a huge set of genetic data from the UK Biobank, a massive database with information from almost 500,000 volunteers, including cancer patients, as well as data from patients from other countries around the world.

They found that patients more likely to produce CyC in response to GCs had a worse overall survival rate.

These patients were also less likely to benefit from treatment, suggesting that CyC production within a tumor may contribute to the failure of cancer immunotherapy.

To confirm CyC’s relationship with cancer, they turned to traditional laboratory work.

In mice, they deleted a CyC-producing gene so that it was no longer present in cancer cells and found that tumors without CyC grew more slowly.

“It is very interesting to approach this issue from multiple angles and corroborate the findings through various approaches”says Meyer.

“Smart genetic models gave us some pointers on which experiments to design to help us answer the question of what this molecule does.” concludes.

Janowitz, who will continue to study CyC, is convinced that this research will greatly help future patients and improve the success of cancer immunotherapy.

Source: EFE