  Currently, most of the basic mechanisms governing tumor-immune system
interactions, in combination with modulations of tumor-associated vasculature,
are far from being completely understood. Here, we propose a mathematical model
of vascularized tumor growth, where the main novelty is the modeling of the
interplay between functional tumor vasculature and effector cell recruitment
dynamics. Parameters are calibrated on the basis of different in vivo
immunocompromised Rag1-/- and wild-type (WT) BALB/c murine tumor growth
experiments. The model analysis supports that tumor vasculature normalization
can be a plausible and effective strategy to treat cancer when combined with
appropriate immuno-stimulations. We find that improved levels of functional
tumor vasculature, potentially mediated by normalization or stress alleviation
strategies, can provide beneficial outcomes in terms of tumor burden reduction
and growth control. Normalization of tumor blood vessels opens a therapeutic
window of opportunity to augment the antitumor immune responses, as well as to
reduce the intratumoral immunosuppression and induced-hypoxia due to vascular
abnormalities. The potential success of normalizing tumor-associated
vasculature closely depends on the effector cell recruitment dynamics and tumor
sizes. Furthermore, an arbitrary increase of initial effector cell
concentration does not necessarily imply a better tumor control. We evidence
the existence of an optimal concentration range of effector cells for tumor
shrinkage. Based on these findings, we suggest a theory-driven therapeutic
proposal that optimally combines immuno- and vaso-modulatory interventions.
