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

激活HRAS突变在皮肤鳞状细胞癌（cSCCs）中经常发生。它们对免疫调节的影响仍不清楚。利用小鼠模型和人类肿瘤材料，我们将探讨在cSCCs中HRAS激活如何介导免疫逃避。我们的目标是：1；了解HRAS的免疫调节作用；2. 评估HRAS、EGFR和免疫抑制代谢物的联合靶向性；探讨高危cSCCs中T细胞衰竭及其与HRAS突变的关系。总的来说，从这些目标中获得的综合知识将转化为对高风险cSCCs的改进和个性化治疗。

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.