Transcriptomic Profiling of Cutaneous Melanoma Metastases Treated With Microwave Ablation-Pilot Study

Microwave ablation induces heating of tissue. High energy results in thermal cell death, but low energy treatment without tissue necrosis has been shown to induce cutaneous immunity in an HPV wart model. It is approved as an effective cancer treatment for solid organ cancers, and therefore it is of interest to know if microwave delivered directly to the skin holds potential for treatment of skin cancer. This pilot study focused on transcriptomic profiling of cutaneous melanoma metastases to investigate molecular changes associated with microwave therapy. Seven adult patients with skin metastases from malignant cutaneous melanoma, not resolving on standard treatment, were recruited. Microwave energy was applied to separate melanoma metastases. Morphological, histological, and transcriptomic changes assessed via tissue RNA sequencing were evaluated. Three participants showed complete response, while four showed partial response by histological assessment. In complete responders, skin lesion RNA sequencing after treatment, compared with baseline, identified increased inflammation (CXCL5, CXCL8, IL1A, COL1A1) and downregulated cancer markers (PRAME, S100B, MLANA, STK32A). Compared with partial responders, complete responders showed enrichment of FABP4 and reduced expression of cancer markers. Microwave therapy produced local tumor responses and associated inflammatory transcriptomic changes in complete responders, supporting further clinical evaluation in cutaneous melanoma metastases.