Antiseptic treatment improves response to topical imiquimod therapy in a UVB-induced non-melanoma skin cancer murine model

Summary: Abstract Body: Each year, 3.3 million Americans are diagnosed with non-melanoma skin cancers (NMSC). While NMSC lesions are effectively treated surgically, many patients with multiple lesions opt for topical treatments, such as imiquimod (IMQ). These therapies are effective but frequently cause significant inflammatory side effects that result in poor treatment adherence and suboptimal clinical outcomes. Our data shows treatment of UVB-induced lesions in a murine model of NMSC with topical IMQ increases the cutaneous microbial inflammatory index, as reflected by decreased Cutibacterium:Staphylococcus ratios. We hypothesized that antimicrobial treatment decreases the side effects of topical IMQ NMSC therapy by reducing the inflammatory cutaneous microbiome. SKH1-ELITE immunocompetent hairless mice with UVB-induced NMSC were treated with oral antibiotics and daily 70% ethanol skin swabs for 2 weeks and then treated daily for 4 weeks with topical antiseptic and 5% IMQ or vehicle. Antiseptic treatment of IMQ treated mice reduced peak weight loss (3.0% vs. 6.5%) and increased the therapeutic response compared to IMQ alone (44.31% vs. 29.09% tumors decreasing in size; p<0.0001). Interestingly, similar trends were observed in vehicle controls. These findings highlight the potential role of the skin microbiome in regulating inflammation in the tumor microenvironment. This work provides a foundation for future research aimed at improving patient outcomes through microbiome-targeted therapies. Kala Mahen¹, Isabel Johnston¹, Alec Minikowski¹, William Massey¹, Naseer Sangwan¹, Vijay Krishna¹, Mark Brown¹, Edward Maytin¹, George Stark¹, Christine McDonald¹ 1. Cleveland Clinic, Cleveland, OH, United States. Innate Immunity, Microbiology, and Microbiome