Single-cell analysis and multiplexed imaging of the metabolic interactions in the tumor immune microenvironment


Cellular metabolism regulates immune cell activation, differentiation and effector functions but current metabolic approaches lack single-cell resolution and simultaneous characterization of cellular phenotype. Here, we developed an approach to characterize the metabolic regulome of single cells together with their phenotypic identity. The method, single-cell metabolic regulome profiling (scMEP), quantifies proteins that regulate metabolic pathway activity using a high-dimensional antibody-based approach. We employed mass cytometry (CyTOF) to benchmark scMEP against bulk metabolic assays by reconstructing the metabolic remodeling of in vitro-activated naïve and memory CD8+ T cells. We applied the approach to clinical samples and identified tissue-restricted, metabolically repressed cytotoxic T cells in human colorectal carcinoma. Combining our method with imaging mass spectrometry (MIBI-TOF), we uncovered the spatial organization of metabolic programs, which indicated exclusion of metabolically repressed immune cells from the tumor-immune boundary. Overall, our approach enables robust approximation of metabolic and functional states in individual cells.


Dr. Hartmann received a BSc and MSc in Molecular Biotechnology from the University of Heidelberg, Germany and his PhD from the University of Zurich, Switzerland for his research on T cell effector functions in human autoimmune diseases. In 2017, he joined Stanford University as a postdoctoral fellow to study anti-tumor immunity and its metabolic regulation. Since 2021, Dr. Hartmann is an independent Group Leader at the German Cancer Research Center (DKFZ), Heidelberg, Germany. His research combines single-cell and imaging proteomic technologies with novel biological assays to reveal interactions of immune cells with their local environment and how these interactions impact clinical outcome in human cancer. Most recently, he has developed a novel approach that enables analysis of cellular metabolism in individual cells and with spatial resolution.

Dr. Hartmann has been the recipient of a Van Riemsdijk PhD Fellowship, a Swiss National Science Foundation Postdoctoral Scholarship, a Novartis Foundation for biomedical research Postdoctoral Fellowship and a European Molecular Biology Organization (EMBO) LongTerm Postdoctoral Fellowship. He has received numerous awards, including a Distinction Award for his Ph.D. Thesis (2016), the Pfizer Research Award (2016), and a Young Investigator Award from the American Association of Immunologists (2019). In 2021, he was awarded with a Young Investigator Grant from the Helmholtz Association.


German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Heidelberg, Germany