A two-phenotype model of immune evasion by cancer cells

• Published in: Journal of theoretical biology 2018-10, Vol.455, p.191-204
• Main Authors: Bayer, Péter, Brown, Joel S., Staňková, Kateřina
• Format: Article
• Language: English
• Subjects: Cancer ecology and evolution; Cancer heterogeneity; Immunoediting; Immunosuppression; Immunotherapy
• ISSN: 0022-5193; 1095-8541
• DOI: 10.1016/j.jtbi.2018.07.014

•A new model of immune evasion links game theory concepts and immune evasion strategies.•The game considers a public goods game between selfish and immunosuppressive, cooperative cancer cells.•The efficacy of treatment options is determined by the transient dynamics within the tumor.•Appealing therapies may be undesirable when they switch the tumor composition from selfish to immunosuppressive cancer cells. We propose a model with two types of cancer cells differentiated by their defense mechanisms against the immune system. “Selfish” cancer cells develop defense mechanisms that benefit the individual cell, whereas “cooperative” cells deploy countermeasures that increase the chance of survival of every cell. Our phenotypes capture the two main features of the tumor’s efforts to avoid immune destruction, crypticity against immune cells for the selfish cells, and tumor-induced immunosuppression for the cooperative cells. We identify steady states of the system and show that only homogeneous tumors can be stable in both size and composition. We show that under generic parameter values, a tumor of selfish cells is more benign than a tumor of cooperative cells, and that a treatment against cancer crypticity may promote immunosuppression and increase cancer growth.