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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."

The Scan

Positive Framing of Genetic Studies Can Spark Mistrust Among Underrepresented Groups

Researchers in Human Genetics and Genomics Advances report that how researchers describe genomic studies may alienate potential participants.

Small Study of Gene Editing to Treat Sickle Cell Disease

In a Novartis-sponsored study in the New England Journal of Medicine, researchers found that a CRISPR-Cas9-based treatment targeting promoters of genes encoding fetal hemoglobin could reduce disease symptoms.

Gut Microbiome Changes Appear in Infants Before They Develop Eczema, Study Finds

Researchers report in mSystems that infants experienced an enrichment in Clostridium sensu stricto 1 and Finegoldia and a depletion of Bacteroides before developing eczema.

Acute Myeloid Leukemia Treatment Specificity Enhanced With Stem Cell Editing

A study in Nature suggests epitope editing in donor stem cells prior to bone marrow transplants can stave off toxicity when targeting acute myeloid leukemia with immunotherapy.