Use of Popular Steroids in Cancer Treatment: Good or Bad?

Steroids are popularly used to regulate the immune response in long-term conditions such as asthma, Crohn’s disease, and even COVID-19. These steroids could also treat cancer treatment side effects and leads to failure of cancer treatment in some patients. The new research by Cold Spring Harbor Laboratory (CSHL) researchers may be closer to answering both questions. Their findings indicate steroids may indirectly lead to some immunotherapy treatment failures by driving the production of a protein called Cystatin C (CyC).

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 (1^✔ ✔Trusted Source
Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy

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What Cancer Patients Need to Know about Steroids

Steroids are very powerful suppressors of immunity and are consequently used to treat autoimmunity, which is when the immune system attacks healthy cells. Researchers have previously shown that steroids can also break cancer immunotherapy. Now, there is perhaps a clue into how they’re doing it.

In the new study, researchers analyzed a massive genetic dataset from the UK Biobank. How massive? Almost 500,000 volunteers, including patients with cancer. They also reached out to researchers overseas to gather even more patient data (2^✔ ✔Trusted Source
Cancer immunotherapy trial registrations increase exponentially but chronic immunosuppressive glucocorticoid therapy may compromise outcomes

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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 (3^✔ ✔Trusted Source
Corticosteroids and Cancer Immunotherapy

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It is powerful to come at this from multiple angles and support the findings through many approaches. Clever genetic models gave us some indication of which experiments to design to help us answer the question of what this molecule does. Researchers are planning to continue studying CyC.

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The research has given them an impetus to find out more about the function of this molecule, specifically in the context of cancer immunotherapy. Perhaps its function can be targeted to enhance the success of cancer immunotherapy.

References:

1. Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy - (https://www.sciencedirect.com/science/article/pii/S2666979X23001222?via%3Dihub)
2. Cancer immunotherapy trial registrations increase exponentially but chronic immunosuppressive glucocorticoid therapy may compromise outcomes - (https://www.annalsofoncology.org/article/S0923-7534(19)32273-2/fulltext)
3. Corticosteroids and Cancer Immunotherapy - (https://aacrjournals.org/clincancerres/article-abstract/doi/10.1158/1078-0432.CCR-22-3181/716400/)

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Source-Eurekalert