Multimodal imaging of the dynamic brain tumor microenvironment during glioblastoma progression and in response to treatment
Anoek Zomer,
Davide Croci,
Joanna Kowal,
Leon van Gurp,
Johanna A. Joyce
Affiliations
Anoek Zomer
Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Centre Lausanne, 1011 Lausanne, Switzerland
Davide Croci
Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Centre Lausanne, 1011 Lausanne, Switzerland
Joanna Kowal
Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Centre Lausanne, 1011 Lausanne, Switzerland
Leon van Gurp
Department of Genetic Medicine and Development, iGE3 and Centre facultaire du diabète, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland
Johanna A. Joyce
Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Centre Lausanne, 1011 Lausanne, Switzerland; Corresponding author
Summary: Tumors evolve in a dynamic communication with their native tissue environment and recruited immune cells. The diverse components of the tumor microenvironment (TME) can critically regulate tumor progression and therapeutic response. In turn, anticancer treatments may alter the composition and functions of the TME. To investigate this continuous dialog in the context of primary brain cancers, we developed a multimodal longitudinal imaging strategy. We combined macroscopical magnetic resonance imaging with subcellular resolution two-photon intravital microscopy, and leveraged the power of single-cell analysis tools to gain insights into the ongoing interactions between different components of the TME and cancer cells. Our experiments revealed that the migratory behavior of tumor-associated macrophages is different in genetically distinct glioblastomas, and in response to macrophage-targeted therapy. These results underscore the importance of studying cancer longitudinally in an in vivo setting, to reveal complex and dynamic alterations in the TME during disease progression and therapeutic intervention.
