A mathematical model for the immunotherapeutic control of the Th1/Th2 imbalance in melanoma

Yuri Kogan; Zvia Agur; Moran Elishmereni

doi:10.3934/dcdsb.2013.18.1017

Article Contents

2013, Volume 18, Issue 4: 1017-1030. Doi: 10.3934/dcdsb.2013.18.1017 open access

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A mathematical model for the immunotherapeutic control of the Th1/Th2 imbalance in melanoma

1.
10 Hate'ena St., P.O.B. 282, Bene Ataroth 60991

Received: April 30, 2012

Revised: July 31, 2012

Published: May 2013

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Abstract

Aggressive cancers develop immune suppression mechanisms, allowing them to evade specific immune responses. Patients with active melanoma are polarized towards a T helper (Th) 2-type immune phenotype, which subverts effective anticancer Th1-type cellular immunity. The pro-inflammatory factor, interleukin (IL)-12, can potentially restore Th1 responses in such patients, but still shows limited clinical efficacy and substantial side effects. We developed a model for the Th1/Th2 imbalance in melanoma patients and its regulation via IL-12 treatment. The model focuses on the interactions between the two Th cell types as mediated by their respective key cytokines, interferon (IFN)-$\gamma$ and IL-10. Theoretical and numerical analysis showed a landscape consisting of a single, globally attracting steady state, which is stable under large ranges of relevant parameter values. Our results suggest that in melanoma, the cellular arm of the immune system cannot reverse tumor immunotolerance naturally, and that immunotherapy may be the only way to overturn tumor dominance. We have shown that given a toxicity threshold for IFN$\gamma$, the maximal allowable IL-12 concentration to yield a Th1-polarized state can be estimated. Moreover, our analysis pinpoints the IL-10 secretion rate as a significant factor influencing the Th1:Th2 balance, suggesting its use as a personal immunomarker for prognosis.

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Mathematics Subject Classification: 92B05, 37N25.

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