The role of HRAS downstream signalling for the production of immunosuppressive metabolites in the microenvironment of HRAS-driven SCC (P13)

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Activating HRAS mutations occur frequently in cutaneous squamous cell carcinomas (cSCCs). Their impact on immune modulation remains poorly defined. Using mouse models and human tumour material, we will address how HRAS activation in cSCCs mediates immune evasion. Our aims are: 1. to understand the immune modulatory actions of HRAS; 2. to evaluate combined targeting of HRAS, EGFR and immunosuppressive metabolites and 3. to investigate T cell exhaustion in high-risk cSCCs and its relation to HRAS mutations. Collectively, the combined knowledge obtained from these aims will be translated into improved and personalized treatment for high-risk cSCCs.