Abstract
Mathematical and computational modelling in oncology has played an
increasingly important role in not only understanding the impact of various
approaches to treatment on tumour growth, but in optimizing dosing regimens and
aiding the development of treatment strategies. However, as with all modelling,
only an approximation is made in the description of the biological and physical
system. Here we show that tissue-scale spatial structure can have a profound
impact on the resilience of tumours to immunotherapy using a classical model
incorporating IL-2 compounds and effector cells as treatment parameters. Using
linear stability analysis, numerical continuation, and direct simulations, we
show that diffusing cancer cell populations can undergo pattern-forming
(Turing) instabilities, leading to spatially-structured states that persist far
into treatment regimes where the corresponding spatially homogeneous systems
would uniformly predict a cancer-free state. These spatially-patterned states
persist in a wide range of parameters, as well as under time-dependent
treatment regimes. Incorporating treatment via domain boundaries can increase
this resistance to treatment in the interior of the domain, further
highlighting the importance of spatial modelling when designing treatment
protocols informed by mathematical models. Counter-intuitively, this mechanism
shows that increased effector cell mobility can increase the resilience of
tumours to treatment. We conclude by discussing practical and theoretical
considerations for understanding this kind of spatial resilience in other
models of cancer treatment, in particular those incorporating more realistic
spatial transport.
Citation
ID:
281568
Ref Key:
prior2025pattern