FIGURE 2.

The mechanisms through which TLRs orchestrate pro‐tumour responses. TLR stimulation activates the NF‐κB cascade, which in turn increases the transcription of inflammatory cytokines including IFN‐α, IL‐1 and IL‐6. Activation of the NF‐κB axis not only promotes anti‐apoptotic factors (Bcl‐XL, Bcl‐2, survivin) but also up‐regulates MMPs which are responsible for the degradation of extracellular matrix. Although TLR4 activation leads to the production of MMP2 and β1‐integrin overexpression, TLR9 stimulation enhances MMP13 level in breast cancer. As represented, increasing of PG‐E2 and COX‐2 by TLR2, TLR4 and TLR9 and phosphorylation of EGFR by TLR4 are the most important mechanisms in TLR‐mediated angiogenesis. Stimulation of TLRs in the tumour microenvironment can provoke tumour cells or tumour‐infiltrating cells to produce suppressor cytokines and chemokines which not only suppress immune cells but also attract more cells to tumour microenvironment—such as MDSC, TAMs and CAFs—to fulfil tumour needs. Finally, TLR downstream signalling can make tumour cells and tumour‐infiltrating cells to switch their metabolic pathway from oxidative phosphorylation to glycolysis