A topical cream developed by researchers at the Perelman School of Medicine at the University of Pennsylvania activated the skin's immune defenses and suppressed tumor growth in two preclinical models of cutaneous squamous cell carcinoma, according to a study published on Mar. 12 in the Journal of Clinical Investigation. The cream works by blocking LSD1, an enzyme that suppresses immune-activating pathways in the skin.
The findings are significant because cutaneous squamous cell carcinoma is one of the most common cancers worldwide, with about a million Americans diagnosed each year. While most cases can be treated with surgery, some tumors metastasize and lead to thousands of deaths annually. Many patients, especially older or immunocompromised individuals, develop numerous precancerous lesions that make repeated surgical procedures difficult.
"What's striking is that a simple topical cream can use the skin's own machinery to recruit and activate immune cells that attack tumors," said Brian C. Capell, MD, PhD, senior author and assistant professor of Dermatology at Penn. "We are carrying out some more studies to refine the formulation this coming year, and we hope to begin a phase 1 clinical trial in the next 1-2 years. Ideally, this cream could be used directly on cancerous and precancerous spots."
The study showed that applying a low-dose topical inhibitor of LSD1 prompted skin cells to signal for immune help by lifting a "brake" on certain immune-activating pathways. Blocking retinoic acid signaling reversed many changes induced by the cream at the skin level, while destroying CD4⁺ T cells eliminated its tumor suppression effect. These results suggest that communication between skin cells and the immune system is key for targeted anti-tumor responses.
Researchers noted that preventing cancer from forming could have an even larger impact than treating existing tumors. An estimated 58 million Americans live with skin precancers or early squamous cell carcinomas each year; a topical treatment could reduce surgeries and lower progression rates to invasive cancer. The team is also exploring whether oral or injectable LSD1 inhibitors might enhance current immunotherapies for advanced cases.
Other authors involved in this research include Nina Kuprasertkul as first author along with several colleagues from Penn Medicine. The work was supported by grants from organizations such as the National Institutes of Health, Damon Runyon Cancer Research Foundation, Dermatology Foundation, and Skin Cancer Foundation.
