A mathematical model of tumor–immune interactions
| Autor: | Mark Robertson-Tessi, Ardith W. El-Kareh, Alain Goriely |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Statistics and Probability
Antigenicity medicine.medical_treatment Cell Biology T-Lymphocytes Regulatory General Biochemistry Genetics and Molecular Biology Immune system T-Lymphocyte Subsets Transforming Growth Factor beta Neoplasms Immune Tolerance medicine Humans IL-2 receptor Immunity Cellular General Immunology and Microbiology Effector Applied Mathematics Models Immunological Immunosuppression Dendritic Cells General Medicine Interleukin-10 Cell biology Interleukin 10 medicine.anatomical_structure Tumor Escape Modeling and Simulation General Agricultural and Biological Sciences |
| Zdroj: | Journal of Theoretical Biology. 294:56-73 |
| ISSN: | 0022-5193 |
| DOI: | 10.1016/j.jtbi.2011.10.027 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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