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23 April 2024 |
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Article overview
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Cancer therapeutic potential of combinatorial immuno- and vaso-modulatory interventions | | H. Hatzikirou
; J. C. L. Alfonso
; S. Muhle
; C. Stern
; S. Weiss
; M. Meyer-Hermann
; | | Date: |
21 May 2015 | | Abstract: | 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 modelling of the
interplay between functional tumor vasculature and effector recruitment
dynamics. Parameters are calibrated on the basis of different in vivo Rag1-/-
and wild-type (WT) BALB/c murine tumor growth experiments. The model analysis
supports that vasculature normalization can be a plausible and effective
strategy to treat cancer when combined with appropriate immuno-stimulation. We
find that improved levels of functional vasculature, potentially mediated by
vascular normalization or stress alleviation strategies, can provide beneficial
outcomes in terms of tumor burden reduction and control. Normalization of tumor
blood vessels opens a therapeutic window of opportunity to augment the anti-
tumor immune responses, as well as to reduce the intratumoral immunosuppression
and hypoxia due to vascular abnormalities. The potential success of normalizing
tumor 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 tumor control, and we evidence the
existence of an optimal effector concentration range for tumor shrinkage. Based
on these findings, we suggest a theory-driven therapeutic proposal that
optimally combines immune- and vaso-modulatory interventions. | | Source: | arXiv, 1505.5670 | | Services: | Forum | Review | PDF | Favorites | |
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