KAUST Grant NumberKUK-C1-013-04
Permanent link to this recordhttp://hdl.handle.net/10754/597300
MetadataShow full item record
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.
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.
SponsorsThis 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).
JournalJournal of Theoretical Biology
CollectionsPublications Acknowledging KAUST Support
- Mechanisms of immune evasion by gliomas.
- Authors: Rolle CE, Sengupta S, Lesniak MS
- Issue date: 2012
- Immunosuppressive strategies that are mediated by tumor cells.
- Authors: Rabinovich GA, Gabrilovich D, Sotomayor EM
- Issue date: 2007
- Activated human CD4+ T cells induced by dendritic cell stimulation are most sensitive to transforming growth factor-beta: implications for dendritic cell immunization against cancer.
- Authors: Lin CM, Wang FH, Lee PK
- Issue date: 2002 Jan
- Immunosuppression induced by immature dendritic cells is mediated by TGF-beta/IL-10 double-positive CD4+ regulatory T cells.
- Authors: Cools N, Van Tendeloo VF, Smits EL, Lenjou M, Nijs G, Van Bockstaele DR, Berneman ZN, Ponsaerts P
- Issue date: 2008 Apr
- Human squamous cell carcinomas evade the immune response by down-regulation of vascular E-selectin and recruitment of regulatory T cells.
- Authors: Clark RA, Huang SJ, Murphy GF, Mollet IG, Hijnen D, Muthukuru M, Schanbacher CF, Edwards V, Miller DM, Kim JE, Lambert J, Kupper TS
- Issue date: 2008 Sep 29