Multiple colonies of cancer involved in mutual suppression with the immune system
Matsuo, K., Hayashi, R. and Iwasa, Y.We study the effects of the immune system on multiple cancer colonies. When cancer cells proliferate, cytotoxic T lymphocytes (CTLs) reactive to the cancer-specific antigens are activated, suppressing the growth of cancer colonies. The immune reaction activated by a large cancer colony may suppress and eliminate smaller colonies. However, cancer cells mitigate immune reactions by slowing down the activation of CTLs in dendritic cells with regulatory T cells and by inactivating CTLs attacking cancer cells with immune checkpoints. If cancer cells strongly suppress the immune reaction, the system may become bistable, where both the cancer-dominated and immunity-dominated states are locally stable. We study several models differing in the distance between colonies and the migration speeds of CTLs and regulatory T cells. We examine how the domains of attraction for multiple equilibria change with parameters. Nonlinear cancer-immunity dynamics may produce a sharp transition from a state with a small number of colonies and strong immunity to one with many colonies and weak immunity, resulting in the rapid emergence of many cancer colonies in the same organ or metastatic sites.
Key Words: Cancer-dominated state, Immunity-dominated state, Immune checkpoint, T cell activation