New research reveals how calcipotriol-plus–5-FU therapy activates immune pathways to prevent squamous cell carcinoma with long-lasting protection.
Study: T helper 2 cell–directed immunotherapy eliminates precancerous skin lesions. Image Credit: Me dia/Shutterstock.com
Skin cancer rates are increasing globally, driving research into new protective treatments. One promising approach is topical immunotherapy with calcipotriol plus 5-fluorouracil (5-FU), which effectively eliminates precancerous skin lesions.
A recent study published in the Journal of Clinical Immunology sheds light on the biological mechanisms behind this therapy.
Immunotherapy for skin cancer
Immunotherapy for cancer is a groundbreaking and effective approach but is often prohibitively expensive and associated with severe side effects. These challenges have spurred research into more affordable and less toxic therapies.
Skin squamous cell carcinoma (SCC), the second most common type of skin cancer, is vulnerable to immune responses even at its precancerous stage. Actinic keratosis (AK), a known risk factor for SCC, can be treated to reduce the risk of progression.
Current AK treatments include topical 5-fluorouracil (5-FU), photodynamic therapy, imiquimod, and tirbanibulin. However, only 5-FU has shown a short-term reduction in SCC risk, which disappears within two years.
This limitation has driven interest in AK immunotherapy as an “innovative and attainable strategy.” Previous research demonstrated that topical calcipotriol combined with 5-FU is highly effective in eliminating AKs, but it lacked insight into its mechanism.
Calcipotriol, a vitamin D analog used to treat psoriasis, increases thymic stromal lymphopoietin (TSLP) levels in keratinocytes. When paired with 5-FU, this effect is amplified, leading to a significant infiltration of