Speaker
Description
Oncolytic viruses interact dynamically with cancer cells, healthy stromal cells, and immune cells in the tumor microenvironment. Therapeutic success therefore depends on the balance between viral spread, infection resistance, and immune activation. In this talk, I will present insights into these interactions using a spatiotemporal computational modeling framework. Our simulations reveal that therapy failure can arise through
multiple mechanisms. For example, even when infection-resistant cancer cells are initially rare, spatial competition can lead to their rapid expansion and tumor persistence. I also find that fast killing of infected cells can paradoxically reduce efficacy by clearing the virus before it spreads, while infection-resistant stromal cells, like macrophages, can further inhibit infection and protect the tumor. Additionally, incorporating immune responses uncovers a fundamental trade-off. Virus-induced signals can enhance T cell-mediated cytotoxicity, but may simultaneously suppress viral amplification by eliminating infected cells too quickly. This leads to stochastic and sometimes counterintuitive outcomes, where treatment timing and delivery strongly affect success. Finally, I will show that macrophages, despite limiting infection, do not necessarily prevent effective therapy. Instead, rationally-engineered viruses to stimulate T cell responses can induce robust anti-tumor immunity even when infection remains spatially constrained. Together, these results highlight how resistance and immune dynamics jointly shape virotherapy outcomes.
Bibliography
@article{Bhatt_Janzen_Daemen_Weissing_2022, title={Modelling the spatial dynamics of oncolytic virotherapy in the presence of virus-resistant tumour cells}, volume={18}, ISSN={1553-7358}, DOI={10.1371/journal.pcbi.1010076}, number={12}, journal={PLoS computational biology}, author={Bhatt, Darshak Kartikey and Janzen, Thijs and Daemen, Toos and Weissing, Franz J.}, year={2022}, month=dec, pages={e1010076}, language={eng} }
@article{Horvathova_Kinderman_Janzen_Hoogeboom_Weissing_VanMontfoort_Daemen_Bhatt_2025, title={Alphavirus replicons encoding IFN-γ enhance cancer virotherapy by overcoming macrophagemediated suppression}, volume={28}, ISSN={25890042}, DOI={10.1016/j.isci.2025.113545}, number={10}, journal={iScience}, author={Horvathova, Laura and Kinderman, Priscilla and Janzen, Thijs and Hoogeboom, Baukje Nynke and Weissing, Franz J. and Van Montfoort, Nadine and Daemen, Toos and Bhatt, Darshak K.}, year={2025}, month=oct, pages={113545}, language={en} }
@article{Bhatt_Janzen_Daemen_Weissing_2024, title={Effects of virus-induced immunogenic cues ononcolytic virotherapy}, volume={14}, ISSN={2045-2322}, url={https://www.nature.com/articles/s41598-024-80542-8}, DOI={10.1038/s41598-024-80542-8}, number={1}, journal={Scientific Reports}, author={Bhatt, Darshak K. and Janzen, Thijs and Daemen, Toos and Weissing, Franz J.}, year={2024}, month=nov, pages={28861}, language={en} }
