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. 2009 Sep;2 Suppl 1(Suppl 1):205-14.
doi: 10.1007/s12307-009-0022-y. Epub 2009 Aug 15.

Cancer Cells Expressing Toll-like Receptors and the Tumor Microenvironment

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Cancer Cells Expressing Toll-like Receptors and the Tumor Microenvironment

Yusuke Sato et al. Cancer Microenviron. 2009 Sep.

Abstract

Toll-like receptors (TLRs) play a crucial role in the innate immune response and the subsequent induction of adaptive immune responses against microbial infection or tissue injury. Recent findings show that functional TLRs are expressed not only on immune cells but also on cancer cells. TLRs play an active role in carcinogenesis and tumor progression during chronic inflammation that involves the tumor microenvironment. Damage-associated molecular patterns (DAMPs) derived from injured normal epithelial cells and necrotic cancer cells appear to be present at significant levels in the tumor microenvironment, and their stimulation of specific TLRs can foster chronic inflammation. This review discusses how carcinogenesis, cancer progression, and site-specific metastasis are related to interactions between cancer cells, immune cells, and DAMPs through TLR activation in the tumor microenvironment.

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Figures

Fig. 1
Fig. 1
TLR signals contribute to tumor progression in the tumor microenvironment. PAMPs derived from microbes and DAMPs derived from injured and necrotic cancer cells might activate TLRs expressed on immune cells and on cancer cells. These activated cells release cytokines and chemokines; the aberrant molecular pattern of chemokines/cytokines might significantly affect the tumor microenvironment. Tregs: regulatory T cells, TAMs: tumor-associated macrophages, DCs: dendritic cells, CAFs: cancer-associated fibroblasts, MDSCs: myeloid-derived suppressor cells
Fig. 2
Fig. 2
TLR3 ligation and subsequent TLR3 mRNA expression in melanoma cells incubated with purified total RNA from normal donor PBLs or allogeneic melanoma cells. When ME7 and ME1 human melanoma cells were incubated 12 h with total RNA from normal PBL and ME5 melanoma cells, mean TLR3 mRNA expression increased 24.6–121.3% as compared with expression in control cells without total RNA
Fig. 3
Fig. 3
During cancer growth and unscheduled cell death, DAMPs derived from necrotic cancer cells might continuously activate TLRs and create a chronic inflammatory condition as well as PAMPs. TLR ligation activates NF-κB and MAPK signaling, causing the production of proinflammatory cytokines and chemokines. The resulting aberrant molecular pattern of cytokines/chemokines might have a crucial role in immunotolerance, maintain tumor microenvironment, tumor angiogenesis that supports tumor progression

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