Figure 1. Schematics of immunoediting.

In the elimination phase, most malignant cells are sensitive to anti-tumor immunity and immunity steps are intact. The elimination of immune-sensitive cells selects for cells with perturbed immunity steps that are no longer sensitive to immune-mediated elimination. There is an evolutionary bottleneck that selects for cells that are either able to evade anti-tumor immunity or can proliferate quickly enough to sustain a high turnover, immune sensitive population. In the equilibrium phase, there is a mixture of immune-sensitive and insensitive cells and tumor cell elimination is proportional to rates of cell proliferation, leading to no net tumor outgrowth. Intact and perturbed immunity steps are both represented during this phase. For tumor outgrowth to occur, immune-insensitive cells are selected for during a second evolutionary bottleneck, allowing for tumor cell proliferation to occur without elimination by anti-tumor immunity. In the escape phase, most malignant cells are insensitive to anti-tumor immunity and immunity steps are perturbed. It is possible for immune-sensitive subclones with intact immunity steps to emerge and/or remain within this population if escaped clones maintain an immunosuppressive environment, thus shielding the sensitive clone from anti-tumor immunity.