Cystatin C Plays Role in Immunosuppression, Cancer Immunotherapy Failure, Study Finds

Cystatin C (CyC), a protease inhibitor, may be involved in immunosuppression and contribute to cancer immunotherapy failure, according to a new Cell Genomics paper. Researchers from Cold Spring Harbor Laboratory in New York noted that CyC is elevated among patients during glucocorticoid (GC) treatment and speculated it could also be associated with disease. They conducted a genome-wide association study using UK Biobank data to generate a polygenic score for CyC production. They further found that both that score and CyC production itself were associated with increased overall and cancer-specific mortality, and that the CyC score predicted immunotherapy failure. In follow-up in vitro, in vivo, and other experiments, the researchers linked CyC to GC signaling, finding that it recruits Trem2+ macrophages and likely contributes to immunotherapy failure. "GCs are very powerful suppressors of immunity and are consequently used to treat autoimmunity," Tobias Janowitz, an assistant professor at CSHL, says in a statement. "We've previously shown that GCs can also break cancer immunotherapy. Now, here's perhaps a clue into how they're doing it."