Development of Novel Biomarkers for Immunotherapy in Neuroblastoma
In addition to standard chemotherapy, surgery and radiation treatment for cancer, immunotherapy, which leads the patient's own immune system to target cancer cells, has been proven effective in some cases and is currently sparking a great deal of interest given its tremendous potential. Immunotherapy agents that target the programmed death 1 (PD-1) and Cytotoxic T-Lymphocyte-associated Antigen 4 (CTLA-4) have recently been approved for melanoma and lung cancer. Despite its promise however, only a small subset of patients have been shown to respond to immunotherapy so far, and it is unknown whether these agents will work for children with cancer. Understanding how exactly the immune system fights pediatric tumors and obtaining biomarkers that can predict an active immune response will greatly advance the use of immunotherapy agents in children. Our lab has developed tools and procedures that may allow such quantification. Our recent results show that immunotherapy combined with radiotherapy can inhibit cancer progression in the mouse models of neuroblastoma.
Here, I propose to use two cutting-edge technologies to monitor how exactly our immune cells attack neuroblastoma: multiplex immunohistochemistry and T-cell receptor repertoire (TCR). These tools will allow us to identify what type of immune cells are involved in the anti-tumor response. We will treat neuroblastoma tumors with radiation therapy and different immune modulating agents such as anti-PD1, anti-CTLA4, or cyclophosphamide, and then utilize these tools to identify the most active immunotherapy regimen.