Handle URI:
http://hdl.handle.net/10754/597300
Title:
A mathematical model of tumor–immune interactions
Authors:
Robertson-Tessi, Mark; El-Kareh, Ardith; Goriely, Alain
Abstract:
A mathematical model of the interactions between a growing tumor and the immune system is presented. The equations and parameters of the model are based on experimental and clinical results from published studies. The model includes the primary cell populations involved in effector T-cell mediated tumor killing: regulatory T cells, helper T cells, and dendritic cells. A key feature is the inclusion of multiple mechanisms of immunosuppression through the main cytokines and growth factors mediating the interactions between the cell populations. Decreased access of effector cells to the tumor interior with increasing tumor size is accounted for. The model is applied to tumors with different growth rates and antigenicities to gauge the relative importance of various immunosuppressive mechanisms. The most important factors leading to tumor escape are TGF-Β-induced immunosuppression, conversion of helper T cells into regulatory T cells, and the limitation of immune cell access to the full tumor at large tumor sizes. The results suggest that for a given tumor growth rate, there is an optimal antigenicity maximizing the response of the immune system. Further increases in antigenicity result in increased immunosuppression, and therefore a decrease in tumor killing rate. This result may have implications for immunotherapies which modulate the effective antigenicity. Simulation of dendritic cell therapy with the model suggests that for some tumors, there is an optimal dose of transfused dendritic cells. © 2011 Elsevier Ltd.
Citation:
Robertson-Tessi M, El-Kareh A, Goriely A (2012) A mathematical model of tumor–immune interactions. Journal of Theoretical Biology 294: 56–73. Available: http://dx.doi.org/10.1016/j.jtbi.2011.10.027.
Publisher:
Elsevier BV
Journal:
Journal of Theoretical Biology
KAUST Grant Number:
KUK-C1-013-04
Issue Date:
Feb-2012
DOI:
10.1016/j.jtbi.2011.10.027
PubMed ID:
22051568
Type:
Article
ISSN:
0022-5193
Sponsors:
This publication is based on the work supported by Award No. KUK-C1-013-04, made by King Abdullah University of Science and Technology (KAUST), and for based in part on the work supported by the National Science Foundation under grants DMS-0907773 (AG). AG is a Wolfson/Royal Society Merit Award Holder. This publication is based on the work supported by the ARCS Foundation, NSF-VIGRE, and the BIO5 Institute at the University of Arizona (MRT).
Appears in Collections:
Publications Acknowledging KAUST Support

Full metadata record

DC FieldValue Language
dc.contributor.authorRobertson-Tessi, Marken
dc.contributor.authorEl-Kareh, Ardithen
dc.contributor.authorGoriely, Alainen
dc.date.accessioned2016-02-25T12:30:10Zen
dc.date.available2016-02-25T12:30:10Zen
dc.date.issued2012-02en
dc.identifier.citationRobertson-Tessi M, El-Kareh A, Goriely A (2012) A mathematical model of tumor–immune interactions. Journal of Theoretical Biology 294: 56–73. Available: http://dx.doi.org/10.1016/j.jtbi.2011.10.027.en
dc.identifier.issn0022-5193en
dc.identifier.pmid22051568en
dc.identifier.doi10.1016/j.jtbi.2011.10.027en
dc.identifier.urihttp://hdl.handle.net/10754/597300en
dc.description.abstractA mathematical model of the interactions between a growing tumor and the immune system is presented. The equations and parameters of the model are based on experimental and clinical results from published studies. The model includes the primary cell populations involved in effector T-cell mediated tumor killing: regulatory T cells, helper T cells, and dendritic cells. A key feature is the inclusion of multiple mechanisms of immunosuppression through the main cytokines and growth factors mediating the interactions between the cell populations. Decreased access of effector cells to the tumor interior with increasing tumor size is accounted for. The model is applied to tumors with different growth rates and antigenicities to gauge the relative importance of various immunosuppressive mechanisms. The most important factors leading to tumor escape are TGF-Β-induced immunosuppression, conversion of helper T cells into regulatory T cells, and the limitation of immune cell access to the full tumor at large tumor sizes. The results suggest that for a given tumor growth rate, there is an optimal antigenicity maximizing the response of the immune system. Further increases in antigenicity result in increased immunosuppression, and therefore a decrease in tumor killing rate. This result may have implications for immunotherapies which modulate the effective antigenicity. Simulation of dendritic cell therapy with the model suggests that for some tumors, there is an optimal dose of transfused dendritic cells. © 2011 Elsevier Ltd.en
dc.description.sponsorshipThis publication is based on the work supported by Award No. KUK-C1-013-04, made by King Abdullah University of Science and Technology (KAUST), and for based in part on the work supported by the National Science Foundation under grants DMS-0907773 (AG). AG is a Wolfson/Royal Society Merit Award Holder. This publication is based on the work supported by the ARCS Foundation, NSF-VIGRE, and the BIO5 Institute at the University of Arizona (MRT).en
dc.publisherElsevier BVen
dc.subjectIL-10en
dc.subjectImmunosuppressionen
dc.subjectRegulatory T cellsen
dc.subjectTGF-Βen
dc.subjectTumor growthen
dc.titleA mathematical model of tumor–immune interactionsen
dc.typeArticleen
dc.identifier.journalJournal of Theoretical Biologyen
dc.contributor.institutionUniversity of Arizona, Tucson, United Statesen
dc.contributor.institutionUniversity of Oxford, Oxford, United Kingdomen
kaust.grant.numberKUK-C1-013-04en
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