A better understanding of the molecular changes involved in the transformation of this UVB-induced carcinoma, from precancerous lesions (actinic keratosis (AK)) to localized cutaneous squamous cell carcinomas (cSCCs) will aid in early detection, development of biomarkers and future targeted treatment strategies. Here we aimed to characterize the molecular and metabolic features of cSCC at different stages of carcinogenesis and their immunologic landscapes. We characterized the large-scale changes in the bioenergetic machinery using a quantitative label-free differential proteomic analysis of human skin samples at different stages of carcinogenesis. The changes in the topology of the metabolic pathways involved were very similar between AK, and peritumoral tissue. The metabolic profile of tumors was significantly different with a dramatic downregulation of the enzymes involved in lipid biosynthesis and a upregulation of several enzymes involved in glycolysis. Specific metabolic modifications, of which some persist throughout tumor development, occur at a very early stage of skin carcinogenesis. We then performed patient derived xenografts of cSCC and noted different tumor behavior with aggressiveness and metastasis in lymph node and lung in some PDX compare to others. To explore immunologic landscapes at different stages of carcinogenesis, single cell RNA sequencing was applied on a premalignant and an aggressive sample of cSCC from the same patient. We uncovered several immune cell subsets depleted in cSCC compared to AK, particularly B and plasma cells, and a specific cluster of macrophages and T cells enriched in the tumor. To conclude, our data suggest that metabolic and immune features of cSCC could be used as pertinent biomarkers for stratification of cSCC.

ESDR251 - Metabolic and immune features as predictive biomarkers of risk stratification of skin carcinoma

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING