Grant: CIHR - ICR / Cancer Research Society Partnership - Research Grants

In Canada, an estimated 5,000 Canadians are diagnosed with head and neck squamous carcinoma and an additional 5,800 patients are diagnosed with lung squamous cell carcinoma (SCC) on an annual basis. There are currently limited treatment options for patients diagnosed with advanced SCCs of the lung and head and neck. Radiotherapy (RT) and immunotherapy are two options that exist, but their efficacy is limited to a small subset of patients. Understanding mechanisms of treatment resistance will provide a new window of opportunity for the majority of SCC patients who fail to respond to treatment. We have shown that RT’s anti-tumor effects can be blunted by mechanisms of immune-suppression including, infiltration of regulatory T cells. We identified the CCL20-CCR6 axis to be activated by radiation and implicated in immune suppression. The overall goal of this research proposal is to dissect the role of CCL20-CCR6 in treatment resistance in SCCs and to test the therapeutic efficacy of its blockade. These studies will have direct implications for improving patient response to RT and for rational design of clinical trials.