System Immunology and Single Cell Biology
Dr. Felix Hartmann
Our research focuses on the crucial interactions within the tissue microenvironment that influence the progression and clinical outcomes of human cancers. We aim to uncover how these interactions affect the behavior of the human immune system, with a particular focus on the metabolic exchanges between T cells, macrophages, and tumor cells, and how these interactions drive immune function and tumor progression.
To investigate these complex interactions, we utilize an innovative proteomic imaging technology known as multiplexed ion beam imaging (MIBI). MIBI allows us to simultaneously quantify over 40 proteins and map their spatial distribution directly in human tissues. We have successfully established MIBI technology at the DKFZ, along with all necessary experimental and analytical workflows. We are now leveraging these capabilities to explore the metabolic regulation of immune cells in clinical tissues. Additionally, we are conducting functional studies on the importance of metabolic pathways using genetic manipulation and human organoid cultures.
Our research integrates the following approaches:
- Systems Immunology: Through multiplexed imaging, we analyze the immune system within human tissues. Collaborating with clinicians, we profile tissue samples from clinical trials targeting various tumor entities, including colorectal carcinoma, melanoma and breast cancer.
- Single-Cell Biology: We develop experimental tools to explore new aspects of cell biology at the single-cell level, particularly the relationship between metabolic reprogramming and epigenetic modifications.
- Computational Biology: In partnership with computational scientists, we apply machine learning techniques to our high-dimensional imaging datasets, leveraging the single-cell and subcellular details to gain deeper insights.
Overall, our lab's goal is to enhance our understanding of the interplay between the immune system and the local tissue structure. By doing so, we aim to contribute to the development of improved immunotherapy treatments for human cancers.
Future projects and goals
Our group uses MIBI-TOF to systematically quantify the heterogeneity, spatial distribution, and clinical relevance of metabolic immune cell states in different human cancer. By employing advanced imaging technologies, we will explore how tumor cells modulate the immune system metabolically and how this affects the immune cells' response to immune checkpoint inhibitor (ICI) therapy. In addtion, our research addresses the mechanistic implications of metabolic rewiring in human tumor organoids.
Overall, we are focusing on
- Metabolic interactions: Provide insights into the metabolic interactions between immune cells and cancer.
- Novel biomarkers: Identify metabolic biomarkers for personalizing treatment strategies.
- Therapeutic targets: Assess metabolic enzymes as therapeutic targets to improve cancer immunotherapy.
In summary, our goal is to enhance the understanding of metabolic interactions in cancer immunology and aid in developing more effective, personalized treatments.
Dr. Felix Hartmann
Junior Group - partner site Heidelberg
DKFZ