TP B.3 - MelBrainSys

Characterizing the immune architecture and the immune modulatory capacity of melanoma brain metastases

The infiltration and activation status of immune cells within tumors and metastases can be crucial for a patient's survival. Hardly anything is known about the immune architecture of brain metastases in melanoma patients and how they are influenced by therapeutic interventions. Hence, the aim of the present sub-project B.3 is to characterize immune cells within melanoma brain metastases. Formalin-fixed and paraffin-embedded as well as fresh melanoma metastases are examined. In addition, there is the unique opportunity to analyze and compare metastases that developed inside and outside a patient's brain. The results are correlated with the clinical-pathological characteristics of melanoma patients in order to identify new prognostic markers. In addition, in vitro studies will characterize the ability of primary cell lines generated from melanoma brain metastases to influence the phenotype and the function of immune cells. The primary tumor cells generated in the sub-project B.2 will be genetically modified, treated with various drugs or established as brain metastases in mice in sub-project B.4. These interventions may influence the expression of immunologically relevant marker molecules and the immunogenicity of the primary tumor cells. The data obtained support the development and testing of a model-based algorithm for the effectiveness of therapies in melanoma patients with brain metastases in sub-project B.1. The requested junior alliance is a close cooperation with medical bioinformatics (B.1), dermato-oncology (B.2) and neuro-oncology (B.4). The goal is to define and validate a model-based algorithm for translational use of system-based predictions to identify innovative, effective and brain-specific therapy strategies for melanoma brain metastases.

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