T-cell conversion from anergic to an activated status upon immunogenic cell death of tumor cells. The activation of tumor-specific T cells is dependent on DCs, which endocytose tumor cell debris and apoptotic vesicles. After intracellular processing the DCs present peptides derived from tumor-associated-antigens in complex with MHC class I molecules to T cells. Without the stimulation by danger-associated molecular patterns (DAMPs), DCs remain immature in a hostile immunosuppressive milieu and anergize CD4+ T cells and cytotoxic T cells (CTLs) resulting in peripheral tolerance. The release of inflammatory factors and the appearance of DAMPs lead to activation of DCs (inflammatory DCs) which subsequently upregulate costimulatory molecules of the B7 family. Inflammatory DCs are able to activate naïve CTLs through MHC I tumor peptide/TCR and B7/CD28 crosslinking. Furthermore, inflammatory DCs can activate naïve CD4+ T cells after MHC class II tumor peptide/TCR and B7/CD28 crosslinking. Activated CD4+ T cells in turn support clonal expansion and activity of CTLs by CD40/CD40L interaction and release of inflammatory cytokines such as IL-2.
