P04 Spatial transcriptomic mapping of melanoma response to microwave therapy
Purevsuren Losol, Andres Vallejo Pulido, Daniel O’Driscoll, Adrian von Witzleben, Matthew Sommerlad, Christian Ottensmeier, Michael Ardern-JonesAbstract
Introduction and aims
Cutaneous melanoma is highly metastatic and resistant to conventional therapies. Its outcomes are shaped by complex genetic and microenvironmental mechanisms that remain incompletely understood. Previous work showed that microwaves can prime keratinocytes to enhance dendritic cell-mediated immune responses, suggesting potential for modulating antitumour immunity. This study aimed to evaluate microwave therapy in melanoma metastases using spatial transcriptomics to identify molecular and cellular signatures associated with treatment response.
Methods
Nine participants with stage IV or inoperable stage III melanoma who were unsuitable for alternative treatments received microwave therapy. Treatment effects were assessed at baseline and three weeks post-treatment, and patients were classified as complete or partial responders based on histological evaluation. Punch biopsies pre- and post-treatment were processed as formalin-fixed paraffin-embedded tissue for 10X Visium spatial transcriptomics. Analyses focused on cell type-specific transcriptional changes and cell–cell interactions relevant to treatment outcomes.
Results
Five major cell clusters were identified: melanoma, keratinocytes, myeloid cells, fibroblasts and inflammatory T/B cells. Complete responders showed strong activation of interferon α/γ pathways, with STAT1, IRF1, IRF9 and NF-κB activated and MYC repressed. VEGFA and HIF signalling suggested a hypoxia-adaptive component. Cell–cell communication analysis revealed major interaction between melanoma-fibroblast in baseline complete responders. Key receptor-ligand associations included ITGB3, SDC2, ERBB3 and ITGB5 in melanoma, CD44 in keratinocytes, LRP1 and ITGA1 in fibroblasts and NTRK1 in immune cells. Post-treatment, MMP7 expression increased in melanoma clusters of complete responders, indicating tissue remodelling.
Conclusions
These results identify melanoma cell programmes associated with treatment response and fibroblasts mediated pathways as potential therapeutic targets and demonstrate the clinical promise of microwave therapy. Our findings underscore the value of spatial transcriptomics for guiding treatment and support further validation in larger patient cohorts.