Specialization
Focus of research
The overall goal of my research team is to uncover the tumor microenvironmental dynamics driving cancer progression to provide novel effective therapies to cancer patients.
During my PhD at the University of Bologna I gained extensive knowledge on bone cancer biology and contributed to unravel the properties and function of mesenchymal stem cells (MSCs) in regenerative medicine and cancer.
Supported by multiple fellowships (including a FIRC fellowship, a Veronesi felloship, a L’Oréal-UNESCO award For Women in Science and two Marie Curie Individual Fellowship), I relocated to the Netherlands in the lab of Michiel Pegtel to resolve the mechanisms of intercellular communication via extracellular vesicles (EVs) in autoimmunity and cancer (Baglio et al., PNAS 2016; Baglio et al., Clin Cancer Res 2017). Here I developed a strong curiosity for the mechanisms by which tumor cells shape a tumor supporting microenvironment.
To identify druggable microenvironmental components driving bone cancer progression, through collaborations with research groups at AmsterdamUMC and the Rizzoli Orthopaedic Institute, I developed a bioluminescent orthotopic model of osteosarcoma, which enabled precise dissection of the interactions between tumor cells and MSCs in the bone marrow environment in vivo. I demonstrated that bone cancer cells are prolific producers of EVs that carry and strongly enhance the activity of TGFβ. Intriguingly, EV-bound TGFβ dramatically alters the immunomodulatory properties of bone marrow MSCs fostering metastasis formation (Baglio et al., Clin Cancer Res 2017).
Based on these studies and supported by a KWF grant selected by the Maarten van der Wijden Foundation, my team has been investigating the mechanisms by which tumor EVs suppress the bone marrow immune environment leading to immune evasion, and whether TGFβ inhibition alone or in combination with cytokine/chemokine receptor (collaboration with Dompe’ Pharmaceutical) and immune checkpoint inhibitors, prevents bone cancer progression in immunocompetent mouse models.
To this purpose we developed an advanced, highly parametric, spectral flow cytometry strategy that allows to detailly address tumor-associated immune alterations and evaluate treatment effects. With this methodology, we discovered that tumor cells growing in the bone drastically alter the bone marrow immune environment, resulting in the accumulation of immune suppressive cell types,
Based on these exciting results, supported by an internal Cancer Center Amsterdam funding, we have recently developed an eighty-marker spectral flow cytometry methodology that can be applied in a liquid biopsy setting as a step towards personalized medicine. This method is unique in that it addresses not only the phenotype, but also the metabolic status of cancer patients’ immune cells, an increasingly recognized indicator of effector function that is completely ignored when relying on traditional flow cytometry methods. For its potential clinical applications this technology has attracted wide interest not only from surrounding scientist and clinicians, but also from pharmaceutical companies, being instrumental for the identification of novel therapeutic strategies and potential companion diagnostics tools.