The funding provided by the European Research Council (ERC) is regarded as an accolade for scientists at all career stages. With its "Starting Grants", the ERC aims to pave the way for excellent young scientists to pursue independent careers. This year, two scientists at the German Cancer Research Center (DKFZ) are receiving the prestigious funding: Felix Hartmann is investigating how the metabolism of tumor and immune cells affects the success of cancer immunotherapies. Marc Zuckermann aims to improve the treatment outcomes of children with malignant brain tumors by combining different therapeutic modalities.
Only a fraction of cancer patients benefit from cancer immunotherapies with so-called immune checkpoint inhibitors. Improving this situation is the goal of research by Felix Hartmann, junior research group leader at DKFZ.
Cellular metabolism has been shown to be a key factor in various immune cell functions, including, for example, the "exhaustion" of T cells, which can then no longer contribute to tumor defense. However, the exact relationships is not completely understood to date. Hartmann postulates that tumors create spatially defined metabolic environments, so-called "metabolic niches", in order to suppress immune cells.
To test this, he wants to identify and quantify the metabolic states of cancer and immune cells. Using a method he has developed, such metabolic studies can be performed in individual cells directly in human tumor tissue. Hartmann plans to combine these analyses with other methods, such as multiplex ion beam imaging, which allows him to visualize a large number of proteins in tumor tissue samples. Using tumor organoids, the researcher also wants to uncover the mechanism of metabolic niche formation.
Hartmann's goal is to use these methods to find out how different tumors influence the metabolism of immune cells to modulate their function. Therapeutic targets may emerge from this analysis, allowing different types of cancer to be treated more successfully with immunotherapies.
Felix Hartmann studied molecular biotechnology at the University of Heidelberg. For his doctoral thesis, he conducted research at the University of Zurich from 2012 to 2016 and moved to Stanford University as a postdoc in 2017. Since 2021, Felix Hartmann has headed the DKTK* junior research group Systems Immunology and Single Cell Biology at DKFZ.
Brain tumors are the most common cause of cancer-related deaths in children. High-grade glioma is the most common malignant brain tumor in children. Standard treatment is usually followed by treatment-resistant relapse and the disease progresses. Experts believe that new combination treatments may improve the prognosis of affected children.
Until now, combination therapies in clinical practice have mostly been limited to radiation and chemotherapy. In contrast, Marc Zuckermann, group leader at the Hopp Children's Tumor Center in Heidelberg, is focusing on multimodal treatment strategies ("4D therapy") to overcome resistance to individual forms of treatment. The theory is that unwanted side effects are thereby distributed among different cell populations, creating a larger therapeutic window.
Zuckermann first wants to combine different drugs with radiotherapy in a comprehensive screening in the laboratory, investigating which agents increase the radiosensitivity of cancer cells. This combination will then be combined in further steps with gene therapies and with cellular immunotherapies (CAR-T cell therapies). Zuckermann plans to test these multimodal approaches in well-established mouse models to predict which combination might best help affected children.
Marc Zuckermann studied cell biology at the University of Osnabrück. For his doctoral thesis, he conducted research at DKFZ from 2012 to 2016. After a research stay at St. Jude Children's Research Hospital in Memphis, USA, he returned to DKFZ in 2019. Since then, Marc Zuckermann has headed the "Preclinical Modeling" group within the Division of Pediatric Neurooncology at DKFZ and KiTZ Heidelberg.
* DKTK: German Cancer Consortium