Interactions between primary melanoma and the immune system:A novel inducible oncogene model

• Applicant: Professorin Stefani Spranger, Ph.D.
• Subject Area: Pathology ; Immunology
• Term: from 2012 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 224607498

Melanoma represents an aggressive cancer and is responsible for the majority of skin cancer-related deaths. Even among clinical responders, resistant disease usually develops following treatment with conventional therapies. Therefore, activating the patient‘s own immune system has the potential to eliminate residual disease and lead to long-term benefit. However, efficacy of immunotherapy is restricted to a subgroup of patients. Correlation analysis has suggested that several gene-alterations are associated with non-inflamed tumors and predict lack of tumor-specific response. These alterations comprise activation of oncogenes, including ý-catenin, Stat-3, and Notch1. Therefore, we intend to explore the crosstalk between designated tumors and the immune system in novel melanoma model systems. An ER-Cre-lox model, using either tyrosinase or Pax3 promotors, enables us to generate tissue-specific melanomas by targeting several oncogene combinations. By employing immunohistochemistry together with gene array technologies, I intend to identify tumor microenvironmental factors and potential secondary mutations associated with the used oncogenes. Moreover, immunological analysis including ELISPOT and skin transplantation onto immunodeficient mice will determine whether specific oncogenes block tumorspecific immune responses. This work will contribute to the development of strategies to select appropriate patients for immunotherapies and to design new therapies to overcome specific genetic alterations in melanoma.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Thomas Gajewski