More than 15% of cancers worldwide have a direct infectious origin [22]. Chronic inflammation appears to be immunologically distinct from acute infection. The acute phase of infection is characterized by CD8+ T-cell priming and activation of NK cells. CD8+ effector T-cells have a central role in tumor-associated antigen (TAA)-specific immunity and thus in elimination of tumors; activated NK cells stimulate the maturation of DCs and facilitate adaptive anti-tumor immunity. The absence or reduction of these functions during chronic inflammation may promote tumor tolerance [23], carcinogenesis and evolution

of GW-572016 in vitro the tumor microenvironment. Chronic inflammation has been thought to induce malignant PF-3084014 in vitro transformation by activation of oncogenes, inhibition of tumor suppressors, and induction of immunosuppression. TLRs are also expressed by cancer cells (Table 2). TLRs selleck chemical expressed on cancer cells can upregulate the NF-κB cascade and produce anti-apoptotic proteins that contribute to carcinogenesis

and cancer cell proliferation. They also can mediate cancer cell release of cytokines and chemokines that can recruit immune cells to enhance immunity in the tumor microenvironment. These optimized immune cells release further proinflammatory cytokines, proangiogenic factors and growth factors, which impair the anti-tumor function of antigen-presenting cells (APCs) and effector T-cells. Table 2 TLR expression in Phloretin human cancer cells Type of cancer TLR Reference citation Gastric cancer TLR2,TLR4,TLR5,TLR9 [9, 24, 44] Colorectal cancer TLR2,TLR3,TLR4,TLR5,TLR9 [4, 25, 26, 47, 69] Ovarian cancer TLR2,TLR3,TLR4,TLR5 [12, 13] Cervical cancer TLR3, TLR4, TLR5,TLR9 [8, 28, 70] Lung cancer TLR2,TLR3,TLR4,TLR9 [6, 33, 71] Prostate cancer TLR4,TLR9 [7, 29]

Melanoma TLR2,TLR3,TLR4 [5, 72] Brain cancer TLR2,TLR4 [3, 73] Breast cancer TLR2,TLR3,TLR4,TLR9 [6, 10, 30] Hepatocellular carcinoma TLR2,TLR3,TLR4,TLR6,TLR9 [11, 70] Laryngeal cancer TLR2,TLR3,TLR4 [74] Contribution of TLR Signals to Carcinogenesis The high risk of gastric cancer in patients with H. pylori-associated chronic gastritis illustrates the link between chronic inflammation and development of cancer [1]. TLR2, 4, 5 and 9 are expressed by normal gastric epithelial cells, and TLR4 signaling has a key role in regulating the proliferation and apoptosis of these cells. However, overexpression of TLR4 has been demonstrated in H. pylori-infected gastric epithelial cells. TLR4, 5 and 9 are strongly expressed not only by gastric cancer cells but also by metaplastic and dysplastic gastric epithelial cells from patients with H. pylori gastritis [9, 24]. Continuous stimulation of these TLRs by the LPS component of H.