Fig. 1.

Schematic description of the requirements for an CD8⁺ T-cell–mediated antitumor immune response. Naïve tumor-specific CD8⁺ T cells can be activated directly from tumor cells or indirectly from APCs presenting TAA. In a second step, differentiation toward a type I phenotype is optimal. This step is favored by IL-12 and IFN-γ and suppressed by IL-4 or IL-13. Furthermore, sufficient expansion of tumor-specific T cells is important and may require IL-2. Activation-induced nonresponsiveness (AINR), anergy induction, and T-cell deletion may interfere with sufficient expansion and in vivo survival. Tumor penetration is influenced by chemokines and adhesion molecules. Furthermore, the interaction between tumor-specific T cells and the tumor cell is improved by high MHC expression, high antigen densitiy on the tumor, and B7 expression of the tumor. Immune escape might be mediated via TGF-β, MHC loss, or engagement of Fas, PD-1, or CTLA-4 on the T cell. Finally, long-term responses require the development of a memory immune response.