How popular steroids could interfere with some cancer treatments (Glucocorticoids increase testable Cystatin C)

Medical Xpress / Cold Spring Harbor Laboratory / Cell Genomics ^ | June 23, 2023 | Tobias Janowitz et al

[ConservativeMind]

Immunotherapy is among the newest and most potent weapons against cancer. It prompts the immune system to recognize tumors as intruders in the body and attack. But not all patients respond well to immunotherapy. Why? Scientists aren't always sure.

Sometimes, immunotherapy patients experience side effects that steroids called glucocorticoids (GCs) can treat. GCs are often used to regulate the immune response in conditions such as asthma, Crohn's disease, and even COVID-19.

Now, researchers indicate GCs may indirectly lead to some immunotherapy treatment failures by driving the production of a protein called Cystatin C (CyC). Higher levels of CyC are linked to poorer outcomes of this type of therapy.

Assistant Professor Tobias Janowitz says, "GCs are very powerful suppressors of immunity and are consequently used to treat autoimmunity," which is when the immune system attacks healthy cells. "We've previously shown that GCs can also break cancer immunotherapy. Now, here's perhaps a clue into how they're doing it."

Janowitz's lab studies the whole-body response to cancer. For this study, he and Sam Kleeman, teamed with Assistant Professor Hannah Meyer, an expert in quantitative biology. Together, they analyzed a massive genetic dataset from the UK Biobank. How massive? Almost 500,000 volunteers, including patients with cancer. Kleeman also reached out to researchers overseas to gather even more patient data.

The scientists found that patients who were 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. This suggests CyC production within a tumor may contribute to the failure of cancer immunotherapy.

To confirm CyC's connection with cancer, the researchers turned to good old-fashioned lab work. In mice, they deleted a CyC-producing gene so it was no longer present in cancer cells. They found that tumors without CyC grew slower.

[ConservativeMind]

I’ve had my Cystatin C tested, to get a more accurate kidney filtration rate.

The test is under $100, and in this case, it tells you if your glucocorticoids are hurting your cancer treatment.

[ConservativeMind]

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