Anti-PD-1 Therapy with Adjuvant Ablative Fractional Laser Improves Anti-Tumor Response in Basal Cell Carcinomas

Abstract

The efficacy of anti-programmedcelldeath1therapy (aPD-1), which was recently approved for basal cell carcinoma (BCC) treatment, can be enhanced by adjuvant ablative fractional laser (AFL) in syngeneic murine tumor models. In this explorative study, we aimed to assess locally applied AFL as an adjuvant to systemic aPD-1 treatment in a clinically relevant autochthonous BCC model. BCC tumors (n = 72) were induced in Ptch1+/−K14-CreER2p53fl/fl-mice (n = 34), and the mice subsequently received aPD-1 alone, AFL alone, aPD-1+AFL, or no treatment. The outcome measures included mouse survival time, tumor clearance, tumor growth rates, and tumor immune infiltration. Both aPD-1 and AFL alone significantly increased survival time relative to untreated controls (31 d and 34.5 d, respectively vs. 14 d, p = 0.0348–0.0392). Complementing aPD-1 with AFL further promoted survival (60 d, p = 0.0198 vs. aPD-1) and improved tumor clearance and growth rates. The BCCs were poorly immune infiltrated, but aPD-1 with adjuvant AFL and AFL alone induced substantial immune cell infiltration in the tumors. Similar to AFL alone, combined aPD-1 and AFL increased neutrophil counts (4-fold, p = 0.0242), the proportion of MHCII-positive neutrophils (p = 0.0121), and concordantly, CD4+ and CD8+ T-cell infiltration (p = 0.0061–0.0242). These descriptive results suggest that the anti-tumor response that is generated by aPD-1 with adjuvant AFL is potentially promoted by increased neutrophil and T-cell engraftment in tumors. In conclusion, local AFL shows substantial promise as an adjuvant to systemic aPD-1 therapy in a clinically relevant preclinical BCC model.

Keywords

• ablative fractional laser
• programmed cell death-1 inhibitor
• basal cell carcinoma
• autochthonous cancer model
• immunotherapy