ERC Consolidator grant awarded to Dr. Maria Tsoumakidou, BSRC Fleming Researcher. The 2-million-euro project is for 5 years.
The European Research Council (ERC) has awarded a prestigious ERC Consolidator grant to Dr. Maria Tsoumakidou. Dr. Tsoumakidou is a board-certified respiratory specialist. Her lab focuses on deciphering the landscape of antigen-presenting cells in cancer. Dr Tsoumakidou is emerging as a leader in the field of stromal immunology for her late discovery of a novel subset of lung fibroblasts that present cancer antigens and provide survival signals to lymphocytes, refuting the conventional assumption that fibroblasts are immunosuppressive. She proposes a new concept in cancer immunity whereby anti-tumor CD4 T cells require interaction with antigen-presenting cells in tumor tissues, where tumor antigens reside.
Maria Tsoumakidou will receive 2 million euro for five years to implement her project artFibro, titled “Artifying fibroblasts: Perturbation modelling in the lung tumor phase space to rewire fibroblasts for immunotherapy”.
Official ERC Press release: European Research Council awards €657m in grants to researchers across Europe | ERC
ERC CoG 2022 | Statistics: https://erc.europa.eu/sites/default/files/2023-01/erc-2022-cog-statistics.pdf
Project Abstract - Lung cancer is the leading cause of cancer death. Immunotherapy improved survival rates, but efficacy is limited to selected patients. We recently discovered universal antigen presenting fibroblasts (apFibros) across human and murine lung tumors and showed that they directly stimulate cancer-specific CD4 T cells, creating immunological hot spots that support immune rejection. These studies achieved a breakthrough on the role of in situ cancer antigen presentation and proposed a novel model whereby tumors can sustain T cells independently of lymph nodes.
Preliminary data suggest that lung apFibros help overcome resistance to checkpoint inhibitors. For their immunotherapeutic exploitation of apFibros two bottlenecks must be overcome: low numbers and incomplete understanding of their configurations. We will integrate computational and laboratory experiments and work in parallel in human and mouse models to generate perturbation datasets across single-cell/cell systems, transcriptomics/epigenomics, spatial/temporal levels, and dissect the molecular landscape that regulates fibroblast states. Our ultimate goal is to unravel perturbations that can diverge cancer-associated fibroblasts to antigen presenting states.
The following questions are at the core of our proposal i) how do diverse fibroblast states emerge and evolve? ii) which gene regulatory networks drive specificity of these states? ii) which are the functional modules that are driven by apFibros and how are they mechanistically explained? iv) how can we transdifferentiate existing fibroblasts to acquire antigen presenting states? v) how can fibroblast reprogramming help overcome immunotherapy resistance?
The proposed research should help advance mechanistic concepts in what we term the “adaptive immune mesenchyme”, decode the complexity of peripheral antigen presentation in tumors and beyond and promote targeting of the stroma for immunotherapy.