Resolving tissue-level proteomic complexity in cutaneous squamous cell carcinoma (cSCC) with ultra high-plex spatial profiling

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Cutaneous squamous cell carcinoma (cSCC) represents a major global health burden. Immune-checkpoint inhibitors (ICIs) are the primary treatment for advanced cSCC with durable responses. However, resistance to ICI is associated with a poor prognosis. More translational methods to profile the tumour microenvironment (TME) are needed. In this study, we demonstrate proof-of-concept for high-plex spatial proteomics 1116 proteins (GeoMx Discovery Protein Atlas, Bruker Spatial Biology) to profile 190 pathology-reviewed, consecutively gridded, tissue-compartments across the tumour and stromal regions revealing expression profiles underscored by metabolic and immunological activity. These signatures differentiate immunocompetent and immunocompromised cSCC patients by varying immune competency, including type I interferon signalling. Taken together, this study demonstrates utility for discovery spatial proteomics in a translationally focussed setting for cSCC.