Analyzing the cancer immunosurveillance hypothesis in human immune organoids

• Applicant: Dr. Tatjana Bilich
• Subject Area: Immunology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 507631106

The cancer immunosurveillance and immunoediting hypotheses describe the interaction of the immune system with malignant cells and suggest that immune cells can fend off or even shape the emerging cancer cells. These theories have been furthered by advancements in tumor immunology and immunotherapy, providing knowledge on how to employ the body’s own defense system to combat malignancies. Despite considerable progress these theories remain unproven, and, to the current knowledge, no one could observe what happens in situ, when a healthy cell becomes malignant. My research project aims to explore this gap using in vitro generated human mini-organs, termed organoids, and is focusing on the following objectives: 1. Establishing a sequence of genetic alterations using non-viral gene editing to induce malignant transformation in lymphocytes and by doing so, mimic hematological malignancies. Multistep malignant transformation enables us to generate cancer clones at different stages of malignancy with varying mutational burden. 2. Evaluate which reporter system or fluorescence-labeled oncogene-specific antibodies to use for tracking transformed cells within the organoid without abrogating possible interactions with the immune system. 3. Determine which immune cell populations, cytokines, and other parameters are part of the reaction against a malignancy upon their first encounter and which technology is best suited to assess this reaction and follow the involved cells in real-time. 4. Establish a readout platform to enable the observation of the immunosurveillance and analyze how the transformed malignant cells and cells of the immune system interact and alter each other’s properties in relation to the mutational burden, stage of malignancy, and concentration of introduced (pre-)malignant cells.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Mark M Davis, Ph.D.