Multiple Factors Determine the Oncolytic or Carcinogenic Effects of TLRs Activation in Cancer

Figure 4

The relationship of some clinically used TLR agonists. TLR agonists stimulate DCs. The activated DC takes up TAA and process it into epitopes. The TAA epitopes are loaded onto MHC-II or MHC-I molecules and presented to T cell receptors on the surface of CD4⁺ or CD8⁺ T cells with the help of costimulatory molecules. For example, the interactions between CD40 with CD40L or CD80/86 with CD28. This stimulates CD4⁺ or CD8⁺ T cells to differentiate into Th1 or cytotoxic lymphocytes (CTLs). The activated Th1 cells release cytokines, e.g., IL-2, IFNγ, and CCL3/4/5. These cytokines instruct CD8⁺ T cells to differentiate into CTLs. The CTLs recognize cancer cells bearing TAA to induce either apoptosis through the interaction of Fas and FasL or necrosis via releasing cytolytic cytokines such as perforin and granzyme B.