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

Figure 3

Involvement of TLR induced proinflammatory cytokines in carcinogenesis. The PAMPs from invading microbes or DAMPs from dying cells engage TLRs or other PRRs to activate NF-κB signaling in immune cells. Consequently, production and release of proinflammatory cytokines such as TNF-α, IL-1, IL-6, IL-11, and IL-8 occur. These proinflammatory cytokines bind to the corresponding receptors in cancer cells to activate NF-κB and STAT3 signaling. The PAMPs and DAMPs can bind TLRs or PRRs on cancer cells. The activation of NF-κB and STAT3 signaling results in a number of mechanisms involved in carcinogenesis such as resistance to chemotherapy, PD-L1 production, accumulation of immunosuppressive cells at the tumor site, generation of cancer stem cells, promotion of cancer cell migration, invasion, and EMT transformation. The clinical effect observed is tumor formation, development, and metastasis. Abbreviations: DAMP, damage-associated molecular pattern; EMT, epithelial-to-mesenchymal transition; IL, interleukin; NF-κB, nuclear factor-κB; PAMP, pathogen-associated molecular pattern; PD-L1, ligand of programed death 1; PRR, pattern recognition receptor; STAT3, signal transducer and activator of transcription 3; TLR, toll-like receptor; and TNF, tumor necrosis factor.