Combination of 5-fluorouracil with photodynamic therapy enhances immune responses in a murine model of actinic keratosis

Photodynamic therapy (PDT) to treat actinic keratoses (AK) involves application of a photosensitizer followed by exposure to light, resulting in effective lesion clearance by inducing cell death and long-term immune responses. Here, we show that pretreatment of AK lesions with 5-fluorouracil (5FU) causes significant enhancement of PDT-related immune effects. SKH-1 mice with AK (generated by repeated UVB exposure) were treated topically with 5FU for three days prior to application of topical ALA followed by blue light exposure. AK lesions were harvested for time-course analyses of intra-tumoral immune responses after PDT with or without 5FU. Immunofluorescence data showed that 5FU pretreatment increased recruitment of innate immune cells, infiltration of activated T cells and of cytotoxic T cells and reduced the presence of cells expressing the immune checkpoint marker PD1. Our results suggest that a combination of 5FU and PDT may synergize to provide better management of AK in the dermatology clinic.