最近的研究表明，烧蚀点阵激光（AFL）可以抑制刺猬通路，增强免疫浸润并清除小鼠模型中的基底细胞癌（BCC）。在这项研究中，我们应用 RNA 测序来进一步表征 AFL 对含有早期微观 BCC 的小鼠皮肤转录组的影响，并将其与局部应用刺猬抑制剂 vismodegib 的效果进行对比。我们的结果表明，小鼠皮肤中 BCC 的诱导主要与基因上调有关（显着上调的基因：277 个，显着下调的基因：24）。通过 Ingenuity Pathway Analysis 对这些基因的表征表明，肿瘤诱导与 BCC 和 Sonic Hedgehog 信号传导的激活相关。 AFL 和 vismodegib 治疗都逆转了这些变化，其中 vismodegib 通过逆转大多数上调基因而表现出卓越的性能（AFL：59/277；vismodegib：180/277）。令人惊讶的是，Ingenuity Pathway Analysis 还显示，AFL 和 vismodegib 治疗均引起大量免疫细胞浸润。基于基因集富集分析和细胞类型解卷积，AFL 治疗导致了最大的免疫细胞募集，两种治疗的免疫细胞募集主要由浸润性中性粒细胞、巨噬细胞和单核细胞组成。总之，AFL 和 vismodegib 治疗后在 BCC 皮肤中观察到的明显效果表明两种干预措施之间存在关键差异。 AFL 或 vismodegib 治疗的未来应用可以利用它们各自的作用，例如将 AFL 对免疫系统的作用与其他局部治疗相结合。© 2024 作者。约翰·威利出版的《实验皮肤病学》

Recent studies have demonstrated that ablative fractional laser (AFL) can inhibit the hedgehog pathway, enhance immune infiltration and clear basal cell carcinomas (BCCs) in murine models. In this study, we applied RNA sequencing to further characterise the impact of AFL on the transcriptome of murine skin containing early-stage microscopic BCCs, contrasting it with the effects of topical application of the hedgehog inhibitor vismodegib. Our results showed that BCC induction in murine skin was primarily linked to gene upregulation (significantly upregulated genes: 277, significantly downregulated genes: 24). Characterisation of these genes with Ingenuity Pathway Analysis showed that tumour induction was associated with activation of BCC and Sonic Hedgehog signalling. Both AFL and vismodegib treatments reversed these changes, with vismodegib demonstrating superior performance by reversing most of the upregulated genes (AFL: 59/277; vismodegib: 180/277). Surprisingly, Ingenuity Pathway Analysis also revealed that both AFL and vismodegib treatments caused considerable immune cell infiltration. Based on gene set enrichment analysis and cell type deconvolution, AFL treatment resulted in the largest immune cell recruitment, which for both treatments primarily consisted of infiltrating neutrophils, macrophages and monocytes. In conclusion, the distinct effects observed in BCC skin following AFL and vismodegib treatment suggest key differences between the two interventions. Future applications of AFL or vismodegib treatments could leverage their individual effects, for example by combining the effect of AFL on the immune system with other topical treatments.© 2024 The Author(s). Experimental Dermatology published by John Wiley & Sons Ltd.