Mathematical modeling of immune modulation by glucocorticoids

Biosystems. 2020 Jan:187:104066. doi: 10.1016/j.biosystems.2019.104066. Epub 2019 Nov 14.

Abstract

The cellular and molecular mechanisms of immunomodulatory actions of glucocorticoids (GC) remain to be identified. Using our experimental findings, a mathematical model based on a system of ordinary differential equations for characterization of the regulation of anti-tumor immune activity by the both direct and indirect GC effects was generated to study the effects of GC treatment on effector CD8+ T cells, GC-generated tolerogenic dendritic cells (DC), regulatory T cells and the growth of lymphoma cells. In addition, we compared the data from in vivo and in silico experiments. The mathematical simulations indicated that treatment with GCs may suppress anti-tumor immune response in a dose-dependent manner. The model simulations were in line with earlier experimental observations of inhibitory effects of GCs on T and NK cells and DCs. The results of this study might be useful for predicting clinical outcomes in patients receiving GC therapy.

Keywords: Anti-tumor response; Glucocorticoids; Immune system; Mathematical model.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Glucocorticoids / immunology
  • Glucocorticoids / pharmacology*
  • Humans
  • Immunosuppressive Agents / immunology
  • Immunosuppressive Agents / pharmacology*
  • Lymphoma / immunology
  • Mice
  • Models, Immunological*
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Glucocorticoids
  • Immunosuppressive Agents