University of Pennsylvania Researchers Develop Topical Cream That Activates Immune Response to Combat Skin Cancer

Penn researchers develop a topical cream blocking LSD1 to activate immune defenses against skin cancer, offering a new hope for non-invasive treatment.

By: AXL Media

Published: Mar 14, 2026, 6:22 AM EDT

Source: Information for this report was sourced from University of Pennsylvania School of Medicine

Lifting the Biological Brakes on Anti-Tumor Immunity

The pursuit of non-surgical interventions for skin cancer has led researchers at the University of Pennsylvania to a breakthrough involving the enzyme LSD1. In a study published in the Journal of Clinical Investigation, scientists demonstrated that a low-dose topical inhibitor can effectively remove the biological "brakes" that normally suppress immune-activating pathways in epidermal cells. By blocking this specific enzyme, the cream prompts skin cells to send out distress signals, recruiting and activating immune cells to attack tumors directly. Senior author Brian C. Capell, MD, PhD, noted that the striking efficiency of the cream lies in its ability to utilize the skin’s own internal machinery to initiate a targeted defense.

Addressing the Burden of Rising Cancer Incidence

Cutaneous squamous cell carcinoma (cSCC) represents one of the most pervasive malignancies globally, with approximately one million Americans diagnosed every year. While surgical excision is the standard of care, the aging population and increased ultraviolet exposure have led to a surge in cases that require more flexible treatment options. For the roughly five percent of patients whose tumors metastasize, the condition can be fatal, resulting in thousands of deaths annually in the United States alone. The burden is particularly heavy for immunocompromised individuals who may develop dozens of lesions, making repeated surgical procedures physically exhausting and clinically impractical.

The Role of T Cells in Tumor Suppression

The efficacy of the Penn-developed cream is deeply rooted in the complex communication between skin cells and the adaptive immune system. The research team found that the suppression of tumor growth was heavily dependent on the presence of CD4+ T cells, a specific type of immune cell. When these cells were removed in preclinical models, the cream’s ability to halt cancer progression was eliminated. This suggests that the therapy functions as a priming mechanism, establishing a critical dialogue between the outer layers of the skin and the body's internal immune response to ensure that anti-tumor actions are both localized and potent.