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Open Access Highly Accessed Research

Immunoediting: evidence of the multifaceted role of the immune system in self-metastatic tumor growth

Heiko Enderling, Lynn Hlatky and Philip Hahnfeldt*

Author Affiliations

Center of Cancer Systems Biology, Steward St. Elizabeth’s Medical Center, Tufts University School of Medicine, 736 Cambridge Street, Boston, MA, 02135, USA

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Theoretical Biology and Medical Modelling 2012, 9:31  doi:10.1186/1742-4682-9-31

Published: 28 July 2012

Abstract

Background

The role of the immune system in tumor progression has been a subject for discussion for many decades. Numerous studies suggest that a low immune response might be beneficial, if not necessary, for tumor growth, and only a strong immune response can counter tumor growth and thus inhibit progression.

Methods

We implement a cellular automaton model previously described that captures the dynamical interactions between the cancer stem and non-stem cell populations of a tumor through a process of self-metastasis. By overlaying on this model the diffusion of immune reactants into the tumor from a peripheral source to target cells, we simulate the process of immune-system-induced cell kill on tumor progression.

Results

A low cytotoxic immune reaction continuously kills cancer cells and, although at a low rate, thereby causes the liberation of space-constrained cancer stem cells to drive self-metastatic progression and continued tumor growth. With increasing immune system strength, however, tumor growth peaks, and then eventually falls below the intrinsic tumor sizes observed without an immune response. With this increasing immune response the number and proportion of cancer stem cells monotonically increases, implicating an additional unexpected consequence, that of cancer stem cell selection, to the immune response.

Conclusions

Cancer stem cells and immune cytotoxicity alone are sufficient to explain the three-step “immunoediting” concept – the modulation of tumor growth through inhibition, selection and promotion.