A joint group of researchers from Humanitas and the University of Eastern Piedmont has identified a new mechanism linking alterations in cholesterol metabolism to cancer progression and immune response, with potential implications for cancer prevention and therapies.

The study, published in the prestigious journal Cancer Discovery, particularly shows how different cancers alter liver cholesterol metabolism, increasing its levels in the blood, and how this cholesterol increase leads to the suppression of the immune response, subsequently promoting cancer growth and spread.

The study was led by Antonio Sica – Head of the Immunometabolism and Tumors laboratory at the IRCCS Humanitas Clinical Institute and Professor at the University of Eastern Piedmont.

The research team also identified the protein – the transcription factor RORγ – that connects the two phenomena: RORγ acts as a sensor capable of detecting elevated cholesterol levels and, consequently, stimulating the production of immunosuppressive cells that hinder the body’s anticancer immune response.

“A particularly significant aspect of the discovery is that drugs commonly used to treat hypercholesterolemia can enhance the effectiveness of cancer immunotherapy, at least in experimental cancer models,” explains Antonio Sica. “This result opens new perspectives for optimizing cancer therapies, particularly for patients who develop resistance to immunotherapeutic treatments.”

These findings reinforce the idea that lipid metabolism and the immune system are deeply interconnected. Understanding these links will allow us to identify new therapeutic targets and more effective strategies to boost the immune response against cancer. It also opens new perspectives for prevention. Altered cholesterol metabolism could represent a risk factor that should be monitored more closely: strategies to control lipid levels could contribute not only to cardiovascular health but also to reducing the risk of developing cancer. Identifying cholesterol-related biomarkers could thus enable earlier diagnoses and targeted preventive interventions.

“Discovering that a drug already available for hypercholesterolemia could improve the effectiveness of cancer immunotherapy is a significant and highly translational result,” concludes Sica. “This research opens new opportunities to integrate metabolic and immunological strategies in the fight against cancer, offering new hope for patients and innovative perspectives for precision medicine.”