2.50
Hdl Handle:
http://hdl.handle.net/10033/620814
Title:
Cancer therapeutic potential of combinatorial immuno- and vasomodulatory interventions.
Authors:
Hatzikirou, H; Alfonso, J C L; Mühle, S; Stern, C; Weiss, S; Meyer-Hermann, Michael ( 0000-0002-4300-2474 )
Abstract:
Currently, most of the basic mechanisms governing tumour-immune system interactions, in combination with modulations of tumour-associated vasculature, are far from being completely understood. Here, we propose a mathematical model of vascularized tumour growth, where the main novelty is the modelling of the interplay between functional tumour 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 tumour growth experiments. The model analysis supports that tumour vasculature normalization can be a plausible and effective strategy to treat cancer when combined with appropriate immunostimulations. We find that improved levels of functional tumour vasculature, potentially mediated by normalization or stress alleviation strategies, can provide beneficial outcomes in terms of tumour burden reduction and growth control. Normalization of tumour blood vessels opens a therapeutic window of opportunity to augment the antitumour immune responses, as well as to reduce intratumoral immunosuppression and induced hypoxia due to vascular abnormalities. The potential success of normalizing tumour-associated vasculature closely depends on the effector cell recruitment dynamics and tumour sizes. Furthermore, an arbitrary increase in the initial effector cell concentration does not necessarily imply better tumour control. We evidence the existence of an optimal concentration range of effector cells for tumour shrinkage. Based on these findings, we suggest a theory-driven therapeutic proposal that optimally combines immuno- and vasomodulatory interventions.
Affiliation:
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38124 Braunschweig, Germany.
Citation:
Cancer therapeutic potential of combinatorial immuno- and vasomodulatory interventions. 2015, 12 (112) J R Soc Interface
Journal:
Journal of the Royal Society, Interface
Issue Date:
6-Nov-2015
URI:
http://hdl.handle.net/10033/620814
DOI:
10.1098/rsif.2015.0439
PubMed ID:
26510827
Type:
Article
Language:
en
ISSN:
1742-5662
Appears in Collections:
publications of the research group system immunology ([BRICS]SIMM)

Full metadata record

DC FieldValue Language
dc.contributor.authorHatzikirou, Hen
dc.contributor.authorAlfonso, J C Len
dc.contributor.authorMühle, Sen
dc.contributor.authorStern, Cen
dc.contributor.authorWeiss, Sen
dc.contributor.authorMeyer-Hermann, Michaelen
dc.date.accessioned2017-02-08T15:27:26Z-
dc.date.available2017-02-08T15:27:26Z-
dc.date.issued2015-11-06-
dc.identifier.citationCancer therapeutic potential of combinatorial immuno- and vasomodulatory interventions. 2015, 12 (112) J R Soc Interfaceen
dc.identifier.issn1742-5662-
dc.identifier.pmid26510827-
dc.identifier.doi10.1098/rsif.2015.0439-
dc.identifier.urihttp://hdl.handle.net/10033/620814-
dc.description.abstractCurrently, most of the basic mechanisms governing tumour-immune system interactions, in combination with modulations of tumour-associated vasculature, are far from being completely understood. Here, we propose a mathematical model of vascularized tumour growth, where the main novelty is the modelling of the interplay between functional tumour 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 tumour growth experiments. The model analysis supports that tumour vasculature normalization can be a plausible and effective strategy to treat cancer when combined with appropriate immunostimulations. We find that improved levels of functional tumour vasculature, potentially mediated by normalization or stress alleviation strategies, can provide beneficial outcomes in terms of tumour burden reduction and growth control. Normalization of tumour blood vessels opens a therapeutic window of opportunity to augment the antitumour immune responses, as well as to reduce intratumoral immunosuppression and induced hypoxia due to vascular abnormalities. The potential success of normalizing tumour-associated vasculature closely depends on the effector cell recruitment dynamics and tumour sizes. Furthermore, an arbitrary increase in the initial effector cell concentration does not necessarily imply better tumour control. We evidence the existence of an optimal concentration range of effector cells for tumour shrinkage. Based on these findings, we suggest a theory-driven therapeutic proposal that optimally combines immuno- and vasomodulatory interventions.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnimalsen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred BALB Cen
dc.subject.meshMice, Knockouten
dc.subject.meshModels, Biologicalen
dc.subject.meshNeoplasms, Experimentalen
dc.subject.meshNeovascularization, Pathologicen
dc.titleCancer therapeutic potential of combinatorial immuno- and vasomodulatory interventions.en
dc.typeArticleen
dc.contributor.departmentBRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38124 Braunschweig, Germany.en
dc.identifier.journalJournal of the Royal Society, Interfaceen

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.