Targeting Toll-like receptors against cancer

Bing Du , Qiu-Li Jiang , Joseph Cleveland , Bing-Rong Liu , Dekai Zhang

Journal of Cancer Metastasis and Treatment ›› 2016, Vol. 2 : 463 -70.

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Journal of Cancer Metastasis and Treatment ›› 2016, Vol. 2:463 -70. DOI: 10.20517/2394-4722.2016.62
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Targeting Toll-like receptors against cancer

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Abstract

The discovery of Toll-like receptors (TLRs) about 20 years ago was a remarkable achievement not only in the field of immunology but also in the field of medicine. The TLRs are a family of pattern recognition receptors which play an important role in immune responses by recognizing pathogen-associated molecular patterns. The TLRs also recognize danger-associated molecular patterns, which are associated with some diseases such as cancer. Recent evidence shows that TLRs are expressed not only in immune cells but also in tumor cells. The TLRs appear to play a role in tumor progression and treatment. Most likely, TLR activation has an impact on the initiation, development and treatment of tumors by modulating the inflammatory microenvironment. However, the activation of TLRs contributes to both inhibition and promotion of various tumors, with unclear underlying mechanisms. In this review article, the authors elucidate their current understanding about the role of TLRs in tumor progression, as well as the recent progress in utilizing TLR agonists as potential therapeutic agents in cancer treatment.

Keywords

Toll-like receptor / innate immunity / cancer / cancer treatment / cancer immunotherapy

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Bing Du, Qiu-Li Jiang, Joseph Cleveland, Bing-Rong Liu, Dekai Zhang. Targeting Toll-like receptors against cancer. Journal of Cancer Metastasis and Treatment, 2016, 2: 463-70 DOI:10.20517/2394-4722.2016.62

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References

[1]

Medzhitov R.Innate immunity: the virtues of a nonclonal system of recognition..Cell1997;91:295-8

[2]

Beutler B.Toll-like receptors: how they work and what they do..Curr Opin Hematol2002;9:2-10

[3]

Akira S,Takeuchi O.Pathogen recognition and innate immunity..Cell2006;124:783-801

[4]

Pandey S,Akira S.Microbial sensing by Toll-like receptors and intracellular nucleic acid sensors..Cold Spring Harb Perspect Biol2015;7:a016246

[5]

Schenten D,Yu S,Lee HK,Pasman L,Wunderlich FT,Zhao H.Signaling through the adaptor molecule MyD88 in CD4+ T cells is required to overcome suppression by regulatory T cells..Immunity2014;40:78-90 PMCID:PMC4445716

[6]

Wang Y,Morin MD,Whitby LR,Huang H,Choi JH,Moresco EM,Zhan X,Boger DL.TLR4/MD-2 activation by a synthetic agonist with no similarity to LPS..Proc Natl Acad Sci U S A2016;113:E884-93

[7]

Kassiotis G.Immune responses to endogenous retroelements: taking the bad with the good..Nat Rev Immunol2016;16:207-19

[8]

Kawai T.Pathogen recognition with Toll-like receptors..Curr Opin Immunol2005;17:338-44

[9]

Maglione PJ,Cunningham-Rundles C.Toll-like receptor signaling in primary immune deficiencies..Ann N Y Acad Sci2015;1356:1-21 PMCID:PMC4629506

[10]

O'Neill LA.Glycolytic reprogramming by TLRs in dendritic cells..Nat Immunol2014;15:314-5

[11]

Santoni M,Sotte V,Lanese A,Piva F,Nabissi M,Cascinu S.Toll like receptors and pancreatic diseases: from a pathogenetic mechanism to a therapeutic target..Cancer Treat Rev2015;41:569-76

[12]

Kawai T.The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors..Nat Immunol2010;11:373-84

[13]

Iwasaki A.Control of adaptive immunity by the innate immune system..Nat Immunol2015;16:343-53 PMCID:PMC4507498

[14]

Shah M,Kim JH.Advances in antiviral therapies targeting Toll-like receptors..Expert Opin Investig Drugs2016;25:437-53

[15]

Takeuchi O,Kawai T,Takada H,Takeda K.Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components..Immunity1999;11:443-51

[16]

Alexopoulou L,Medzhitov R.Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3..Nature2001;413:732-8

[17]

Poltorak A,Smirnova I,Van Huffel C,Birdwell D,Silva M,Freudenberg M,Layton B.Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene..Science1998;282:2085-8

[18]

Hayashi F,Ozinsky A,Yi EC,Eng JK,Underhill DM.The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5..Nature2001;410:1099-103

[19]

Heil F,Hochrein H,Kirschning C,Lipford G,Bauer S.Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8..Science2004;303:1526-9

[20]

Kanzler H,Hessel EM.Therapeutic targeting of innate immunity with Toll-like receptor agonists and antagonists..Nat Med2007;13:552-9

[21]

Zhang D,Hayden MS,Bussey C,Ghosh S.A toll-like receptor that prevents infection by uropathogenic bacteria..Science2004;303:1522-6

[22]

O'Neill LA.The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling..Nat Rev Immunol2007;7:353-64

[23]

Curtin JF,Candolfi M,Assi H,Edwards MR,Kroeger KM,Muhammad AK,Arditi M,Ribas A,Castro MG.HMGB1 mediates endogenous TLR2 activation and brain tumor regression..PLoS Med2009;6:e10

[24]

Ribeiro RA,Wong DV,Leite CA,Cunha FQ.Irinotecan- and 5-fluorouracil-induced intestinal mucositis: insights into pathogenesis and therapeutic perspectives..Cancer Chemother Pharmacol2016;78:881-93

[25]

Kuo WT,Yu LC.Eritoran suppresses colon cancer by altering a functional balance in Toll-like receptors that bind lipopolysaccharide..Cancer Res2016;76:4684-95

[26]

Prakash H,Singh S.CD14/TLR4 priming potentially recalibrates and exerts anti-tumor efficacy in tumor associated macrophages in a mouse model of pancreatic carcinoma..Sci Rep2016;6:31490 PMCID:PMC4980608

[27]

Llitjos JF,Alby-Laurent F,Merdji H,Toubiana J,Mira JP,Chiche JD.Sepsis-induced expansion of granulocytic myeloid-derived suppressor cells promotes tumour growth through Toll-like receptor 4..J Pathol2016;239:473-83

[28]

Fukata M,Vamadevan AS,Breglio K,Hsu D,Harpaz N,Subbaramaiah K,Itzkowitz SH.Toll-like receptor-4 promotes the development of colitis-associated colorectal tumors..Gastroenterology2007;133:1869-81

[29]

Furrie E,Thomson G.Toll-like receptors-2, -3 and -4 expression patterns on human colon and their regulation by mucosal-associated bacteria..Immunology2005;115:565-74 PMCID:PMC1782176

[30]

Zhou M,Funk HM,Mounajjed T.Toll-like receptor expression in normal ovary and ovarian tumors..Cancer Immunol Immunother2009;58:1375-85

[31]

Kelly MG,Chen R,Abrahams VM,Visintin I,Mor G.TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer..Cancer Res2006;66:3859-68

[32]

Niedzielska I,Tkacz M,Ziaja K,Mazurek U.Toll-like receptors and the tendency of normal mucous membrane to transform to polyp or colorectal cancer..J Physiol Pharmacol2009;60 Suppl 1:65-71

[33]

Seki E.Toll-like receptors and adaptor molecules in liver disease: update..Hepatology2008;48:322-35

[34]

Naugler WE,Kim S,Kim K,Karin M.Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production..Science2007;317:121-4

[35]

Husseinzadeh N.Role of toll-like receptors in cervical, endometrial and ovarian cancers: a review..Gynecol Oncol2014;135:359-63

[36]

Belmont L,Antoine M,Guignabert C,Cadranel J.Expression of TLR9 in tumor-infiltrating mononuclear cells enhances angiogenesis and is associated with a worse survival in lung cancer..Int J Cancer2014;134:765-77

[37]

Luo Y,Wu JY,Zhang WJ,Shi Z.Regulation of migration and invasion by Toll-like receptor-9 signaling network in prostate cancer..Oncotarget2015;6:22564-74 PMCID:PMC4673182

[38]

Paone A,Galli R,De Cesaris P,Ziparo E.Toll-like receptor 3 triggers apoptosis of human prostate cancer cells through a PKC-alpha-dependent mechanism..Carcinogenesis2008;29:1334-42

[39]

Taura M,Suico MA,Koga T,Sato T,Kai H.TLR3 induction by anticancer drugs potentiates poly I: C-induced tumor cell apoptosis..Cancer Sci2010;101:1610-7

[40]

Salaun B,Matikainen S,Romero P.Toll-like receptor 3 expressed by melanoma cells as a target for therapy?.Clin Cancer Res2007;13:4565-74

[41]

Cai Z,Shi Z,Liu M.Activation of Toll-like receptor 5 on breast cancer cells by flagellin suppresses cell proliferation and tumor growth..Cancer Res2011;71:2466-75 PMCID:PMC3074302

[42]

Li X,Liu X,Zhou W,Cen Y,Cao G,Pang X,Zheng J.CpG ODN107 potentiates radiosensitivity of human glioma cells via TLR9-mediated NF-kappaB activation and NO production..Tumour Biol2012;33:1607-18

[43]

Damiano V,Formisano L,Gelardi T,Cozzolino I,Agrawal S,De Placido S,Tortora G.Toll-like receptor 9 agonist IMO cooperates with everolimus in renal cell carcinoma by interfering with tumour growth and angiogenesis..Br J Cancer2013;108:1616-23 PMCID:PMC3668470

[44]

Shi M,Liu L,Han F,Wang F,Li Y.MAP1S Protein Regulates the Phagocytosis of Bacteria and Toll-like Receptor (TLR) Signaling..J Biol Chem2016;291:1243-50 PMCID:PMC4714212

[45]

Yuminamochi E,Takeda K,Okumura K.Interleukin-12- and interferon-gamma-mediated natural killer cell activation by Agaricus blazei Murill..Immunology2007;121:197-206 PMCID:PMC2265935

[46]

Sharma S,Davoodi M,Lee JM,Salgia R.TLR3 agonists and proinflammatory antitumor activities..Expert Opin Ther Targets2013;17:481-3 PMCID:PMC3758767

[47]

Sfondrini L,Besusso D,Tagliabue E,Balsari A.Antitumor activity of the TLR-5 ligand flagellin in mouse models of cancer..J Immunol2006;176:6624-30

[48]

Prins RM,Bruhn KW,Koya RC,Miller JF.The TLR-7 agonist, imiquimod, enhances dendritic cell survival and promotes tumor antigen-specific T cell priming: relation to central nervous system antitumor immunity..J Immunol2006;176:157-64

[49]

Kortylewski M,Herrmann A,Kowolik C,Lee H,Liu Y,Deng J,Raubitschek A,Rossi JJ,Jove R.In vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist enhances antitumor immune responses..Nat Biotechnol2009;27:925-32 PMCID:PMC2846721

[50]

Davis MB,Fu J,Pardoll D.Intratumoral administration of TLR4 agonist absorbed into a cellular vector improves antitumor responses..Clin Cancer Res2011;17:3984-92 PMCID:PMC3117911

[51]

Geng D,Srivastava R,Velasco-Gonzalez C.When Toll-like receptor and T-cell receptor signals collide: a mechanism for enhanced CD8 T-cell effector function..Blood2010;116:3494-504 PMCID:PMC2981476

[52]

Salaun B,Rissoan MC,Renno T.TLR3 can directly trigger apoptosis in human cancer cells..J Immunol2006;176:4894-901

[53]

Estornes Y,Virard F,Pierrot A,Bonnin M,Mercier-Gouy P,Salaun B,Micheau O.dsRNA induces apoptosis through an atypical death complex associating TLR3 to caspase-8..Cell Death Differ2012;19:1482-94 PMCID:PMC3422471

[54]

Fucikova J,Urbanova L,Kepp O,Salek C,Kroemer G,Spisek R.Prognostic and predictive value of DAMPs and DAMP-associated processes in cancer..Front Immunol2015;6:402 PMCID:PMC4528281

[55]

Jin Y,Choi MH,Bae YM.Regulation of anti-inflammatory cytokines IL-10 and TGF-beta in mouse dendritic cells through treatment with Clonorchis sinensis crude antigen..Exp Mol Med2014;46:e74

[56]

Luddy KA,Tafreshi NK,Morse DL.The role of toll-like receptors in colorectal cancer progression: evidence for epithelial to leucocytic transition..Front Immunol2014;5:429 PMCID:PMC4202790

[57]

Kaczanowska S,Davila E.TLR agonists: our best frenemy in cancer immunotherapy..J Leukoc Biol2013;93:847-63 PMCID:PMC3656332

[58]

Huang B,Li H,Chen Y,Mayer L,Xiong H.Toll-like receptors on tumor cells facilitate evasion of immune surveillance..Cancer Res2005;65:5009-14

[59]

Medzhitov R,Janeway CAJr.A human homologue of the Drosophila Toll protein signals activation of adaptive immunity..Nature1997;388:394-7

[60]

Vacchelli E,Sautes-Fridman C,Zitvogel L,Galluzzi L.Trial watch: Toll-like receptor agonists for cancer therapy..Oncoimmunology2013;2:e25238

[61]

Jinesh GG.Redirecting neutrophils against bladder cancer cells by BCG and Smac mimetic combination..Oncoimmunology2012;1:1161-2 PMCID:PMC3494630

[62]

Bidnur S,Black PC.Inhibiting immune checkpoints for the treatment of bladder cancer..Bladder Cancer2016;2:15-25 PMCID:PMC4927995

[63]

Holcmann M,Sibilia M.How imiquimod licenses plasmacytoid dendritic cells to kill tumors..Oncoimmunology2012;1:1661-3 PMCID:PMC3525638

[64]

Paavonen J,Salmeron J,Chow SN,Kitchener H,Teixeira JC,Hedrick J,Limson G,Szarewski A,Aoki FY,Poppe WA,Jenkins D,Zahaf T,Struyf F,Dubin G.Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women..Lancet2009;374:301-14

[65]

Salaun B,Asselin-Paturel C,Chemin K,Massacrier C,Chenard MP,Goubar A,Pierres M,Romero P.TLR3 as a biomarker for the therapeutic efficacy of double-stranded RNA in breast cancer..Cancer Res2011;71:1607-14

[66]

Chochi K,Kinoshita M,Shinomiya N,Kawabata T,Ono S,Mochizuki H.Helicobacter pylori augments growth of gastric cancers via the lipopolysaccharide-toll-like receptor 4 pathway whereas its lipopolysaccharide attenuates antitumor activities of human mononuclear cells..Clin Cancer Res2008;14:2909-17

[67]

Mittal D,Venereau E,Bianchi ME.TLR4-mediated skin carcinogenesis is dependent on immune and radioresistant cells..EMBO J2010;29:2242-52 PMCID:PMC2905255

[68]

Thuringer D,Benikhlef N,Bouchot A,Solary E.Transactivation of the epidermal growth factor receptor by heat shock protein 90 via Toll-like receptor 4 contributes to the migration of glioblastoma cells..J Biol Chem2011;286:3418-28 PMCID:PMC3030348

[69]

Fukata M,Santaolalla R,Pastorini C,Ungaro R,Cooper HS,Kosco-Vilbois M,Perez MT,Vamadevan AS,Abreu MT.Constitutive activation of epithelial TLR4 augments inflammatory responses to mucosal injury and drives colitis-associated tumorigenesis..Inflamm Bowel Dis2011;17:1464-73 PMCID:PMC3117047

[70]

Bauer AK,DeGraff LM,Walker CR,Kleeberger SR.Toll-like receptor 4 in butylated hydroxytoluene-induced mouse pulmonary inflammation and tumorigenesis..J Natl Cancer Inst2005;97:1778-81

[71]

Zhao S,Zhang Q.Zhang D. Toll-like receptors and prostate cancer..Front Immunol2014;5:352 PMCID:PMC4107957

[72]

Rakoff-Nahoum S.Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88..Science2007;317:124-7

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