Tumor Clearance Analysis on a Cancer Chemo-Immunotherapy Mathematical Model

Bull Math Biol. 2019 Oct;81(10):4144-4173. doi: 10.1007/s11538-019-00636-7. Epub 2019 Jul 1.

Abstract

Mathematical models may allow us to improve our knowledge on tumor evolution and to better comprehend the dynamics between cancer, the immune system and the application of treatments such as chemotherapy and immunotherapy in both short and long term. In this paper, we solve the tumor clearance problem for a six-dimensional mathematical model that describes tumor evolution under immune response and chemo-immunotherapy treatments. First, by means of the localization of compact invariant sets method, we determine lower and upper bounds for all cells populations considered by the model and we use these results to establish sufficient conditions for the existence of a bounded positively invariant domain in the nonnegative orthant by applying LaSalle's invariance principle. Then, by exploiting a candidate Lyapunov function we determine sufficient conditions on the chemotherapy treatment to ensure tumor clearance. Further, we investigate the local stability of the tumor-free equilibrium point and compute conditions for asymptotic stability and tumor persistence. All conditions are given by inequalities in terms of the system parameters, and we perform numerical simulations with different values on the chemotherapy treatment to illustrate our results. Finally, we discuss the biological implications of our work.

Keywords: Chemo-immunotherapy; Global stability; Tumor clearance; Tumor persistence.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Proliferation / drug effects
  • Combined Modality Therapy
  • Computer Simulation
  • Humans
  • Immunotherapy
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Mathematical Concepts
  • Mice
  • Models, Biological*
  • Neoplasms / immunology
  • Neoplasms / pathology*
  • Neoplasms / therapy*
  • Nonlinear Dynamics
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology