UC San Diego

Patients with metastatic and locally advanced cutaneous squamous cell carcinoma (CuSCC) undergoing anti-programmed death-1(PD-1) immune checkpoint blockade therapy have shown durable anti-tumor activity. Response to anti-PD-1 checkpoint blockade therapy partially depends on an existing anti-tumor T cell population within the tumor microenvironment (TME) directed against neoantigens specific for the tumor. The development and ultimately escape from this immune response is not well understood in cutaneous squamous cell cancer development. Using gene expression profiles including those that predict response to anti-PD-1 therapy, I will investigate normal skin to precancerous skin to invasive CuSCC from both immunocompetent and immunocompromised patients with quantitative molecular profiling of metabolic pathway and immune related gene expression. We expect to show differential expression of genes involved in shaping the TME and immune cell infiltration from normal skin to invasive cancer. Therefore, these findings can help identify steps in cancer development and perhaps insight into prevention strategies. In addition, we will compare the development of tumors in the context of a normal immune system and an impaired immune response (ie organ transplant patients). We hope these profiles may help identify additional therapeutic strategies for treating both immune competent and immune suppressed patients.