Figure 1.

Processes to activate T cell immunity against cancer: In the lymph node, T cell priming occurs through mature dendritic cells (DCs) presenting tumor-derived antigens. The number of arising T helper (T_H) cells and cytotoxic T cells (CTL) is limited through cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). Antibodies against CTLA-4 allow for activation of more T cells due to the amelioration of negative signals during T-cell priming. In addition, anti-CTLA-4 inhibits Treg which express high levels of CTLA-4 constitutively. Activated T cells migrate into the tumor milieu where they engage with tumor cells expressing peptide-MHC that can be recognized by the T cell receptor (TCR). TCR-pMHC interaction will activate tumor cell killing processes unless suppression occurs through concomitant PD-1/PD-L1 interaction. Killing of tumor cells can occur if the negative signaling is blocked through anti-PD-1 or anti-PD-L1 antibodies. NK cells can recognize tumor cells that express low or no MHC and, thus, cooperate with CTL to prevent tumor escape. If tumor cell killing occurs, antigen is released which can be taken up by immature DCs. Immature DCs can mature to mature DCs which then present antigen to T cells in the lymph node, leading to the generation of new tumor-reactive T cells. If the natural process of antigen presentation does not occur (efficiently), therapeutic vaccination using ex vivo generated antigen-loaded DCs or peptides may be applied.