title: Mathematical models of immune-induced cancer dormancy and the emergence of immune evasion.
abstract: Cancer dormancy, a state in which cancer cells persist in a host without significant growth, is a natural forestallment of progression to manifest disease and is thus of great clinical interest. Experimental work in mice suggests that in immune-induced dormancy, the longer a cancer remains dormant in a host, the more resistant the cancer cells become to cytotoxic T-cell-mediated killing. In this work, mathematical models are used to analyse the possible causative mechanisms of cancer escape from immune-induced dormancy. Using a data-driven approach, both decaying efficacy in immune predation and immune recruitment are analysed with results suggesting that decline in recruitment is a stronger determinant of escape than increased resistance to predation. Using a mechanistic approach, the existence of an immune-resistant cancer cell subpopulation is considered, and the effects on cancer dormancy and potential immunoediting mechanisms of cancer escape are analysed and discussed. The immunoediting mechanism assumes that the immune system selectively prunes the cancer of immune-sensitive cells, which is shown to cause an initially heterogeneous population to become a more homogeneous, and more resistant, population. The fact that this selection may result in the appearance of decreasing efficacy in T-cell cytotoxic effect with time in dormancy is also demonstrated. This work suggests that through actions that temporarily delay cancer growth through the targeted removal of immune-sensitive subpopulations, the immune response may actually progress the cancer to a more aggressive state.
authors: Center of Cancer Systems Biology, GRI, Saint Elizabeth's Medical Center , Tufts University School of Medicine , 736 Cambridge Street, CBR1, Boston, MA 02135 USA.
authors: Kathleen P
authors: KP
authors: Wilkie
authors: Center of Cancer Systems Biology, GRI, Saint Elizabeth's Medical Center , Tufts University School of Medicine , 736 Cambridge Street, CBR1, Boston, MA 02135 USA.
authors: Philip
authors: P
authors: Hahnfeldt
keywords: cancer dormancy; immunoediting; mathematical model