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      Toll-Like Receptors and Cancer, Particularly Oral Squamous Cell Carcinoma

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          Abstract

          It is becoming increasingly apparent that the tumor microenvironment plays an important role in the progression of cancer. The microenvironment may promote tumor cell survival and proliferation or, alternatively may induce tumor cell apoptosis. Toll-like receptors (TLRs) are transmembrane proteins, expressed on immune cells and epithelial cells, that recognize exogenous and endogenous macromolecules. Once activated, they initiate signaling pathways leading to the release of cytokines and chemokines, which recruit immune cells inducing further cytokine production, the production of angiogenic mediators and growth factors, all of which may influence tumor progression. This paper examines the actions of TLRs in carcinogenesis with particular emphasis on their role in oral squamous cell carcinoma.

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          Most cited references65

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          Toll-like receptors: critical proteins linking innate and acquired immunity.

          Recognition of pathogens is mediated by a set of germline-encoded receptors that are referred to as pattern-recognition receptors (PRRs). These receptors recognize conserved molecular patterns (pathogen-associated molecular patterns), which are shared by large groups of microorganisms. Toll-like receptors (TLRs) function as the PRRs in mammals and play an essential role in the recognition of microbial components. The TLRs may also recognize endogenous ligands induced during the inflammatory response. Similar cytoplasmic domains allow TLRs to use the same signaling molecules used by the interleukin 1 receptors (IL-1Rs): these include MyD88, IL-1R--associated protein kinase and tumor necrosis factor receptor--activated factor 6. However, evidence is accumulating that the signaling pathways associated with each TLR are not identical and may, therefore, result in different biological responses.
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            NF-kappaB in cancer: from innocent bystander to major culprit.

            Nuclear factor of kappaB (NF-kappaB) is a sequence-specific transcription factor that is known to be involved in the inflammatory and innate immune responses. Although the importance of NF-KB in immunity is undisputed, recent evidence indicates that NF-kappaB and the signalling pathways that are involved in its activation are also important for tumour development. NF-kappaB should therefore receive as much attention from cancer researchers as it has already from immunologists.
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              Therapeutic targeting of innate immunity with Toll-like receptor agonists and antagonists.

              The identification of the antigen recognition receptors for innate immunity, most notably the Toll-like receptors, has sparked great interest in therapeutic manipulation of the innate immune system. Toll-like receptor agonists are being developed for the treatment of cancer, allergies and viral infections, and as adjuvants for potent new vaccines to prevent or treat cancer and infectious diseases. As recognition grows of the role of inappropriate Toll-like receptor stimulation in inflammation and autoimmunity, significant efforts have begun to develop antagonists to Toll-like receptors as well.
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                Author and article information

                Contributors
                URI : http://frontiersin.org/people/u/166495
                URI : http://frontiersin.org/people/u/183242
                URI : http://frontiersin.org/people/u/184155
                URI : http://frontiersin.org/people/u/184331
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                24 September 2014
                2014
                : 5
                : 464
                Affiliations
                [1] 1Faculty of Dentistry, Sir John Walsh Research Institute, University of Otago , Dunedin, New Zealand
                [2] 2Faculty of Dentistry, Department of Oral Pathology and Oral Medicine, National University of Malaysia , Kuala Lumpur, Malaysia
                Author notes

                Edited by: Anahid Jewett, University of California, Los Angeles, USA

                Reviewed by: Ruipeng Wang, National Institutes of Health, USA; Eliana Ruggiero, German Cancer Research Center, Germany; Manel Juan, Hospital Clínic, Spain

                *Correspondence: Alison Mary Rich, Faculty of Dentistry, Sir John Walsh Research Institute, University of Otago, PO Box 647, Dunedin 9054, New Zealand e-mail: alison.rich@ 123456otago.ac.nz

                This article was submitted to Tumor Immunity, a section of the journal Frontiers in Immunology.

                Article
                10.3389/fimmu.2014.00464
                4174116
                25309546
                a57b611a-0666-4540-b4f6-370e33a76c07
                Copyright © 2014 Rich, Hussaini, Parachuru and Seymour.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 29 June 2014
                : 10 September 2014
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 80, Pages: 6, Words: 5624
                Categories
                Immunology
                Mini Review

                Immunology
                toll-like receptors,tlr,nf-κb,oral squamous cell carcinoma
                Immunology
                toll-like receptors, tlr, nf-κb, oral squamous cell carcinoma

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