Immunoediting: evidence of the multifaceted role of the immune system in self-metastatic tumor growth
Year: 2012
Type: article
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.
Authors: Heiko Enderling, Lynn Hlatky, Philip Hahnfeldt
Institutions: Tufts University, St. Elizabeth's Medical Center
Language: English
Subfield: Modeling and Simulation
Field: Mathematics
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $2,590
Awards: NEW; TITLE: MULTI-SCALE SYSTEMS BIOLOGY OF LOW-DOSE CARCINOGENESIS RISK; PI: LYNN HLATKY, NEW; TITLE: MULTI-SCALE SYSTEMS BIOLOGY OF LOW-DOSE CARCINOGENESIS RISK; PI: LYNN HLATKY, IMPLICATIONS OF POPULATION HETEROGENEITY FOR LOW-DOSE RISK, IMPLICATIONS OF POPULATION HETEROGENEITY FOR LOW-DOSE RISK
OpenAlex ID: W2160400298
