Spatial computational modelling illuminates the role of the tumour microenvironment for treating glioblastoma with immunotherapies.

Abstract

Glioblastoma is the most common and deadliest brain tumour in adults, with a median survival of 15 months under the current standard of care. Immunotherapies like immune checkpoint inhibitors and oncolytic viruses have been extensively studied to improve this endpoint. However, most thus far have failed. To improve the efficacy of immunotherapies to treat glioblastoma, new single-cell imaging modalities like imaging mass cytometry can be leveraged and integrated with computational models. This enables a better understanding of the tumour microenvironment and its role in treatment success or failure in this hard-to-treat tumour. Here, we implemented an agent-based model that allows for spatial predictions of combination chemotherapy, oncolytic virus, and immune checkpoint inhibitors against glioblastoma. We initialised our model with patient imaging mass cytometry data to predict patient-specific responses and found that oncolytic viruses drive combination treatment responses determined by intratumoral cell density. We found that tumours with higher tumour cell density responded better to treatment. When fixing the number of cancer cells, treatment efficacy was shown to be a function of CD4 + T cell and, to a lesser extent, of macrophage counts. Critically, our simulations show that care must be put into the integration of spatial data and agent-based models to effectively capture intratumoral dynamics. Together, this study emphasizes the use of predictive spatial modelling to better understand cancer immunotherapy treatment dynamics, while highlighting key factors to consider during model design and implementation.