A mathematical model of tumor-immune interactions

Mark Robertson-Tessi, Ardith El-Kareh Fox, Alain Goriely

Research output: Contribution to journalArticle

47 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)56-73
Number of pages18
JournalJournal of Theoretical Biology
Volume294
DOIs
StatePublished - Feb 7 2012

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Tumors
Tumor
Theoretical Models
mathematical models
Mathematical Model
Mathematical models
neoplasms
T-cells
Interaction
Neoplasms
Dendritic Cells
T-lymphocytes
immunosuppression
dendritic cells
Immunosuppression
Cell Population
Immune System
Regulatory T-Lymphocytes
Immune system
Helper-Inducer T-Lymphocytes

Keywords

  • IL-10
  • Immunosuppression
  • Regulatory T cells
  • TGF-Β
  • Tumor growth

ASJC Scopus subject areas

  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Modeling and Simulation
  • Statistics and Probability
  • Applied Mathematics

Cite this

A mathematical model of tumor-immune interactions. / Robertson-Tessi, Mark; Fox, Ardith El-Kareh; Goriely, Alain.

In: Journal of Theoretical Biology, Vol. 294, 07.02.2012, p. 56-73.

Research output: Contribution to journalArticle

Robertson-Tessi, Mark ; Fox, Ardith El-Kareh ; Goriely, Alain. / A mathematical model of tumor-immune interactions. In: Journal of Theoretical Biology. 2012 ; Vol. 294. pp. 56-73.
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