STIC-GBM · Spatio-temporal dynamics of immune circuitry in glioblastoma: from single cells to comprehensive models of tumor niches
Horizon Europe — Marie Skłodowska-Curie Actions
- Duration
- 2024-04-01 → 2026-04-30
- EU contribution
- €173,847
- Participants
- 2
- Scheme
- HORIZON-TMA-MSCA-PF-EF
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Results in brief
Spatio-temporal dynamics of immune circuitry in glioblastoma: from single cells to comprehensive models of tumor niches
Glioblastoma is among the most aggressive malignant brain tumours in adults and remains associated with limited treatment options and poor survival. While immunotherapies have transformed treatment in several cancers, their success in glioblastoma has been limited. A major reason is the highly complex and immunosuppressive tumour microenvironment, in which immune cells are progressively reprogrammed and prevented from mounting effective anti-tumour responses. STIC-GBM addressed this challenge by combining single-cell genomics, spatial transcriptomics, antibody-based single-cell technologies, computational modelling and functional perturbation approaches. The overall objective was to understand how immune escape develops in glioblastoma across space and time, and to identify cellular programmes or molecular regulators that may be relevant for future therapeutic strategies. The project had four main scientific objectives: to develop a spatio-temporal single-cell approach for studying immune cell infiltration into glioma; to generate computational methods for analysing spatial tissue niches; to establish workflows for applying these methods to glioma patient material; and to functionally validate candidate regulators of tumour-associated immune programmes. The pathway to impact combines biological discovery with technological innovation. By generating new methods for analysing complex single-cell and spatial data, the project supports data-driven biomedical research beyond glioblastoma. Its results are relevant for cancer immunology, spatial biology and computational biology, and contribute to the broader European objective of strengthening digital and AI-supported life-science research.
Data: CORDIS, © European Union
Project objective
Glioblastoma (GBM) is the most lethal brain malignancy in adults and is associated with a poor prognosis. Therapy options in GBM patients are largely limited by the highly immunosuppressive tumor microenvironment (TME). Identifying and disrupting these immunosuppressive communication circuits between immune cells and the tumor is key to reinvigorate the immune system’s ability to fight the tumor. Here, we combine my previous experience in the analysis of single cell data at the neuro-immune interface with Prof. Zeiser’s patient-centered expertise in developing novel therapy options to combat tumor immune escape. In this highly complementary setting, we propose a data-driven approach to trace and perturb inhibitory communication circuits elicited by the TME across space and time with the aim to discover novel immunotherapeutic targets in GBM. Using a novel temporal single cell technology, we will 1) assemble a multi-layered spatio-temporal single cell roadmap to characterize and model how individual immune cells are affected by the TME in a murine model of GBM. 2) We will develop a computational framework for spatial transcriptomics to dissect single cells into niches defined by similar interaction programs with neighboring cells. 3) Using this tool, we will quantify the niche organization in human patients and identify ligand-receptor interaction pairs crucial for niche maintenance. 4) Candidate genes will be genetically ablated in either the tumor or the immune compartment and evaluated with regards to their in vivo efficacy in suppressing tumor growth. Our cutting-edge analytical pipeline from the identification of driver molecules for immune escape to the assessment of in vivo efficacy in a preclinical model of GBM will reveal novel targets for treatment. Our study thereby works directly towards the Horizon Europe Mission to understand, treat and beat cancer.
Original text from CORDIS.
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Data: CORDIS, © European Union