Grant: CIHR Fellowship

Head and neck squamous cell carcinoma (HNSCC) describes a collection of squamous cell cancers (SCC) arising in the head and neck region. HNSCC is associated with significant morbidity and mortality due to the fact that treatment options for patients with late-stage metastatic disease are limited to radiation and chemotherapy. New and effective therapies are urgently needed to help improve the lives of individuals with HNSCC. Development of novel therapeutic options relies on understanding the mechanisms that contribute to progression of HNSCC. Recent evidence indicates that interactions between tumor cells and cells of the immune system, including antibody-producing cells (B cells) and cells with direct and specific killing function (T cells), may play a role in the development of HNSCC. For example, our previous studies revealed that antibodies secreted from B cells promote the development of SCC in mouse models. In addition, it is now known that the presence of molecules that suppress the killing activity of T cells have been associated with tumor progression. The studies proposed here use mouse models of SCC as tools to study HNSCC. We will examine the hypothesis that new therapeutic approaches that target the tumor-promoting properties of B cells and also inhibit T cell suppression can improve chemotherapy responses and reduce tumor burden. Results from our research may reveal novel therapeutic targets for treatment of HNSCC. Importantly this pre-clinical modeling is being performed alongside a phase 2 proof-of-concept clinical trial evaluating whether therapeutic targeting of both B and T cell pathways slows tumor progression in patients with advanced HNSCC. We anticipate that data generated from these studies will be crucial for identifying biomarkers that stratify patients based on their likelihood to respond to therapy and will guide clinical trials by aiding the ability of clinicians to monitor disease progression, regression and/or remission.