The Impact of Widely Used Steroids on Cancer Treatments

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. Yet just how they work is also a mystery.

Now, Cold Spring Harbor Laboratory (CSHL) researchers may be closer to answering both questions. Their new research indicates 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.

For this study, the researchers analyzed a massive genetic dataset from the UK Biobank. How massive? Almost 500,000 volunteers, including patients with cancer and they 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.

Reference: Cystatin C is glucocorticoid-responsive, directs the recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy, Cell Genomics, DOI 10.1016/j.xgen.2023.100347