title: Cancer immunoediting: A process driven by metabolic competition as a predator-prey-shared resource type model.
abstract: It is a well-established fact that tumors up-regulate glucose consumption to meet increasing demands for rapidly available energy by upregulating a purely glycolytic mode of glucose metabolism. What is often neglected is that activated cytotoxic cells of the immune system, integral players in the carcinogenesis process, also come to rely on glycolysis as a primary mode of glucose metabolism. Moreover, while cancer cells can revert back to aerobic metabolism, rapidly proliferating cytotoxic lymphocytes are incapable of performing their function when adequate resources are lacking. Consequently, it is likely that in the tumor microenvironment there may exist competition for shared resources between cancer cells and the cells of the immune system, which may underlie much of tumor-immune dynamics. Proposed here is a model of tumor-immune-glucose interactions, formulated as a predator-prey-common resource type system. The outcome of these interactions ranges from tumor elimination, to tumor dormancy, to unrestrained tumor growth. It is also predicted that the process of tumor escape can be preceded by periods of oscillatory tumor growth. A detailed bifurcation analysis of three subsystems of the model suggest that oscillatory regimes are a result of competition for shared resource (glucose) between the predator (immune cells) and the prey (cancer cells). Existence of competition for nutrients between cancer and immune cells may provide additional mechanistic insight as to why the efficacy of many immunotherapies may be limited.
authors.affiliation: Newman Lakka Institute, Floating Hospital for Children at Tufts Medical Center, Boston, MA 02111, United States. Electronic address: Irina.Kareva@tufts.edu.
authors.forename: Irina
authors.initials: I
authors.lastname: Kareva
authors.affiliation: Department of Mathematics, Howard University, Washington, DC 20059, United States.
authors.forename: Faina
authors.initials: F
authors.lastname: Berezovskaya
mesh_terms: D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism; D011235:Predatory Behavior; D019139:Tumor Escape
keywords: Cancer ecology; Cancer metabolism; Immune suppression; Immunoediting; Mathematical model; Predator–prey; Warburg effect