Objective The bone marrow (BM) represents the prime location in which cancer cells survive aggressive treatments. This poses a major health challenge because the mortality rate of patients with curable cancer doubles if tumor cells persist in the BM. One unresolved question is why the immune system fails to eradicate cancer cells from this microenvironment even though it represents a lymphatic organ. Surprisingly, despite the ongoing revolution in immune oncology, the regulation and potential therapeutic activation of the immune response in the BM still remains largely unexplored. In this grant application a new line of research is proposed with the overall objective of understanding the cellular and molecular mechanisms, which control anti-cancer immune responses in the BM. The originality of this proposal relates to the hypothesis that innate and adaptive immune cells are suppressed by stroma cells in the BM. Therefore, we will conduct a comprehensive phenotypic and functional profiling of immune and stroma cells in the BM of cancer patients with and without persisting tumor cells. Based on these insights we will develop novel strategies to harness the immune system to eliminate malignant cells from the BM. The ground-breaking nature of the project is that it will shed light on the unappreciated immune microenvironment in the BM. Its specific strength lies in the multidisciplinary design encompassing informative patient cohorts, state-of-the-art mouse models and cutting-edge technologies including Next-Generation-Sequencing as well as innovative drug candidates. Hereby I can build on my internationally recognized expertise in the BM microenvironment field, which has already led to the successful development of a clinical-stage drug. Novel strategies to eliminate malignant cells from the bone marrow are of utmost medical importance because they would increase the cure rate of cancer patients. Fields of science medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverysocial sciencessociologydemographymortalitysocial sciencespolitical sciencespolitical transitionsrevolutionsmedical and health sciencesbasic medicineimmunologymedical and health sciencesclinical medicineoncology Keywords tumor-stroma interactions bone marrow stroma minimal residual disease breast cancer acute myeloid leukemia immune oncology Axl Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2017-STG - ERC Starting Grant Call for proposal ERC-2017-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Host institution DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG Net EU contribution € 737 450,00 Address IM NEUENHEIMER FELD 280 69120 Heidelberg Germany See on map Region Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 737 450,00 Beneficiaries (2) Sort alphabetically Sort by Net EU contribution Expand all Collapse all DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG Germany Net EU contribution € 737 450,00 Address IM NEUENHEIMER FELD 280 69120 Heidelberg See on map Region Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 737 450,00 UNIVERSITAETSKLINIKUM HAMBURG-EPPENDORF Germany Net EU contribution € 753 375,00 Address Martinistrasse 52 20251 Hamburg See on map Region Hamburg Hamburg Hamburg Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 753 375,00
