A study published in the Journal of Clinical Investigation reports that a topical cream developed by researchers at the Perelman School of Medicine at the University of Pennsylvania activated immune defenses in the skin and suppressed tumor growth in two preclinical models of cutaneous squamous cell carcinoma (cSCC). The findings were announced on Mar. 13 by the research team, who say the cream works by blocking LSD1, an enzyme that suppresses immune-activating pathways.
The development is significant because cSCC is one of the most common cancers worldwide, with about a million Americans diagnosed each year. While surgery is effective for most cases, up to five percent of tumors metastasize, leading to thousands of deaths annually. Many patients, especially older or immunocompromised individuals, develop numerous precancerous lesions that make repeated surgical procedures difficult.
Senior author Brian C. Capell, MD, PhD, assistant professor of Dermatology at Penn, said: “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.” Capell added that further studies are underway to refine the formulation and that a phase 1 clinical trial could begin within one to two years. "Ideally, this cream could be used directly on cancerous and precancerous spots," he said.
The study found that inhibiting LSD1 lifted a "brake" on certain immune-activating pathways in epidermal cells. This prompted skin cells to signal for immune help and played a key role in slowing tumor growth. Blocking retinoic acid signaling reversed many changes induced by the cream, while destroying CD4⁺ T cells eliminated its tumor suppression effect—suggesting communication between skin cells and the immune system is crucial for targeted anti-tumor responses.
Researchers note that preventing cancer from forming could have an even larger impact than treating existing cases. 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 cSCC.
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 and various foundations.
