Figure 1. Activation versus suppression during tumor progression.

Immune activation during early tumor progression may be triggered by the expression of neoantigens. In addition, the progressive growth of tumors may be associated with the invasion and destruction of surrounding normal tissues. Other factors that may cause immune activation include generation of heat shock proteins (Hsps), which result from cellular stress, and ROS such as OH⁻ and H₂O₂. Conversely, immune activation and function may be hampered by a lack of appropriate costimulation, the presence of immunosuppressive cytokines (for example, VEGF, IL-10 and TGF-β), and the impact of immunoregulatory cells such as CD4⁺CD25⁺ T cells and NKT cells. As tumors grow, these events occur in the presence of massive apoptosis and necrosis of tumor cells, infiltrating immune cells and surrounding stromal cells. The fate of tumors may be dictated by the net effect of immune activation and immune inhibition.