Mathematical modeling and analysis of combinational immune boost for tumor elimination

摘要

The immune system has an ability to recognize tumor as non-self antigen, and initiates inflammatory response to eliminate tumor. A dendritic cell (DCs) population is one of immune cell subsets that specifically uptakes foreign antigen and then presents to T cells. Dendritic cell boost ex vivo is operated to enhance immune response against tumor that in general comes to fail due to several complex reasons. Although dendritic cell therapy has been operated in clinical trials by boosting tumor immune responses, less is known about dynamic behaviors generated by interactions among immune cell subsets and tumor cells. In this paper, we construct and analyze a mathematical model describing tumor killing by T cells activated by dendritic cells. A handling time representing a waiting time required for T cells to be activated during antigen presentation is incorporated in our model. Mathematical analyses imply that successful tumor elimination depends on the amount of T cells activated ex vivo when introduced. Moreover, numerical simulations imply that an immune escape basin in which tumor can escape from T cell responses increases when the handling time increases, indicating that efficient tumor elimination might result in immediate T cell inactivation due to rapid decline of antigenic stimulation.