FIGURE 3.

The mechanisms through which TLRs orchestrate anti‐tumour responses. TLR3 signalling can up‐regulate JNK and p38 which play important roles in regulation and induction of apoptosis. Moreover, TLR3 stimulation can take the control of p53 transcription and caspase cascade through up‐regulation of IFN‐γ. TLR9 activation, on the other hand, up‐regulates Bax which inserts into mitochondria membrane and makes it permeable to cytochrome C that is capable to initiate caspase‐dependent apoptosis. Because of the high‐level expression of TLRs on DCs, TLR agonists can make these cells present TAAs to T cells optimally. Activated DCs, in turn, could activate NK cells by secretion of type I IFNs and using INAM‐INAM interaction. On the other hand, activation of MDSCs by TLR7, 9 agonists inhibit their suppressor effects, leading to their maturation into APCs with the ability to elicit T cell anti‐tumour response. Moreover, stimulation of TLRs not only stops inhibitory functions of Tregs via IL‐6 induction but also suppresses their recruitment to the tumour microenvironment. Finally, stimulation of TLR3 with poly I:C up‐regulates TNF‐α that induces M1 macrophage phenotype with an important role in tumour regression