Toll-like receptor immune modulatory role in personalized management of colorectal cancer, review of literature

References

• Chen H, Jiang Z. The essential adaptors of innate immune signaling. Protein Cell. 2013;4(1):27–39.
   PubMed Web of Science ®Google Scholar
• Zhai Y, Wang C, Jiang Z. Cross-talk between bacterial PAMPs and host PRRs. Natl Sci Rev. 2018;5(6):791–792.
   Web of Science ®Google Scholar
• Kumar H, Kawai T, Akira S. Pathogen recognition by the innate immune system. Int Rev Immunol. 2011;30(1):16–34.
   PubMed Web of Science ®Google Scholar
• Takeda K, Akira S. Toll-like receptors. Current Protocols Immunol. 2015;109:14.2. 1–2. 0.
   PubMedGoogle Scholar
• Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell. 2010;140(6):805–820.
   PubMed Web of Science ®Google Scholar
• He L, Liu Y, Lai W, et al. DNA sensors, crucial receptors to resist pathogens, are deregulated in colorectal cancer and associated with initiation and progression of the disease. J Cancer. 2020;11(4):893.
   PubMed Web of Science ®Google Scholar
• Parlato M, Yeretssian G. NOD-like receptors in intestinal homeostasis and epithelial tissue repair. Int J Mol Sci. 2014;15:9594–9627.
   PubMed Web of Science ®Google Scholar
• Castaño-Rodríguez N, Kaakoush NO, Mitchell HM. Pattern-recognition receptors and gastric cancer. Front Immunol. 2014;5:336.
   PubMed Web of Science ®Google Scholar
• Moaaz M, Youssry S, Moaz A, et al. Study of Toll-like receptor 4 gene polymorphisms in colorectal cancer: correlation with clinicopathological features. Immunol Invest. 2020;Jan 30,49:5, 571–584.
   PubMed Web of Science ®Google Scholar
• Pancione M, Giordano G, Remo A, et al. Immune escape mechanisms in colorectal cancer pathogenesis and liver metastasis. J Immunol Res. 2014 Jan 1;2014:686879.
   PubMed Web of Science ®Google Scholar
• Lasry A, Zinger A, Ben-Neriah Y. Inflammatory networks underlying colorectal cancer. Nat Immunol. 2016;17:230–240.
   PubMed Web of Science ®Google Scholar
• Shi Y, Li Z, Zheng W, et al. Changes of immunocytic phenotypes and functions from human colorectal adenomatous stage to cancerous stage: update. Immunobiology. 2015;220:1186–1196.
   PubMed Web of Science ®Google Scholar
• Medvedev AE. Toll-like receptor polymorphisms, inflammatory and infectious diseases, allergies, and cancer. J Interferon Cytokine Res. 2013;33(9):467–484.
   PubMed Web of Science ®Google Scholar
• Medzhitov R. Damage control in host–pathogen interactions. Proc Nat Acad Sci. 2009;106(37):15525–15526.
   PubMed Web of Science ®Google Scholar
• Takeda K, Akira S. Toll-like receptors. Curr Protoc Immunol. 2007;Chapter 14:Unit 14. 12.
   PubMedGoogle Scholar
• Skevaki C, Pararas M, Kostelidou K, et al. Single nucleotide polymorphisms of Toll‐like receptors and susceptibility to infectious diseases. Clin Exp Immunol. 2015;180(2):165–177.
   PubMed Web of Science ®Google Scholar
• Yarovinsky F, Zhang D, Andersen JF, et al. TLR11 activation of dendritic cells by a protozoan profilin-like protein. Science. 2005;308:1626–1629.
   PubMed Web of Science ®Google Scholar
• Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity. 2011;34(5):637–650.
   PubMed Web of Science ®Google Scholar
• Beutler B. Microbe sensing, positive feedback loops, and the pathogenesis of inflammatory diseases. Immunol Rev. 2009;227:248–263.
   PubMed Web of Science ®Google Scholar
• O’Neill LA, Bowie AG. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol. 2007;7:353–364.
   PubMed Web of Science ®Google Scholar
• Burns K, Martinon F, Esslinger C, et al. MyD88, an adapter protein involved in interleukin-1 signaling. J Biol Chem. 1998;273:12203–12209.
   PubMed Web of Science ®Google Scholar
• O’Neill LA. When signaling pathways collide: positive and negative regulation of toll-like receptor signal transduction. Immunity. 2008;29:12–20.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Zarrabi K, Hou W, et al. Assessing clinical outcomes in colorectal cancer with assays for invasive circulating tumor cells. Biomedicines. 2018;6(2):69.
   Web of Science ®Google Scholar
• Semlali A, Almutairi M, Pathan AAK, et al. Toll-like receptor 6 expression, sequence variants, and their association with colorectal cancer risk. J Cancer. 2019;10(13):2969–2981. DOI:10.7150/jca.31011
   PubMed Web of Science ®Google Scholar
• Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86.
   PubMed Web of Science ®Google Scholar
• Marques I, Araujo A, de Mello RA. Anti-angiogenic therapies for metastatic colorectal cancer: current and future perspectives. World J Gastroenterol. 2013;19:7955–7971.
   PubMed Web of Science ®Google Scholar
• Jeon J, Du M, Schoen RE, et al. Determining risk of colorectal cancer and starting age of screening based on lifestyle, environmental, and genetic factors. Gastroenterology. 2018;154(8):2152–2164.
   PubMed Web of Science ®Google Scholar
• Pancione M, Remo A, Colantuoni V. Genetic and epigenetic events generate multiple pathways in colorectal cancer progression. Patholog Res Int. 2012;2012(11):509348.
   PubMedGoogle Scholar
• McAllister SS, Weinberg RA. The tumour-induced systemic environment as a critical regulator of cancer progression and metastasis. Nat Cell Biol. 2014;16:717–727.
   PubMed Web of Science ®Google Scholar
• Barker HE, Paget JT, Khan AA, et al. The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence. Nat Rev Cancer. 2015;15:409–425.
   PubMed Web of Science ®Google Scholar
• Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252–264.
   PubMed Web of Science ®Google Scholar
• CS G, Giannakis M, Wells DK, et al. Genetic mechanisms of immune evasion in colorectal cancer. Cancer Discov. 2018;8(6):730–749. DOI:10.1158/2159-8290.CD-17-1327
   PubMed Web of Science ®Google Scholar
• Kloor M, Michel S, von Knebel Doeberitz M. Immune evasion of microsatellite unstable colorectal cancers. Int J Cancer. 2010;127(5):1001–1010.
   PubMed Web of Science ®Google Scholar
• Semlali A, Alnemari R, Almalki E, et al. Gene polymorphism and susceptibility to cancer development. Genetic Diversity Dis Susceptibility. 2018;57. DOI:10.5772/intechopen.78029.
   Google Scholar
• Rakoff-Nahoum S, Medzhitov R. Toll-like receptors and cancer. Nat Rev Cancer. 2009;9:57–63.
   PubMed Web of Science ®Google Scholar
• Terzić J, Grivennikov S, Karin E, et al. Inflammation and colon cancer. Gastroenterology. 2010;138(6):2101–2114.
   PubMed Web of Science ®Google Scholar
• Hawn TR, Misch EA, Dunstan SJ, et al. A common human TLR1 polymorphism regulates the innate immune response to lipopeptides. Eur J Immunol. 2007;37(8):2280–2289. DOI:10.1002/eji.200737034
   PubMed Web of Science ®Google Scholar
• Okazaki S, Loupakis F, Stintzing S, et al. Clinical significance of TLR1 I602S polymorphism for patients with metastatic colorectal cancer treated with FOLFIRI plus bevacizumab. Mol Cancer Ther. 2016;15(7):1740–1745. DOI:10.1158/1535-7163.MCT-15-0931
   PubMed Web of Science ®Google Scholar
• Semlali A, Parine NR, Al-Numair NS, et al. Potential role of Toll-like receptor 2 expression and polymorphisms in colon cancer susceptibility in the Saudi Arabian population. Onco Targets Ther. 2018;11:8127–8141.
   PubMed Web of Science ®Google Scholar
• Slattery ML, Herrick JS, Bondurant KL, et al. Toll-like receptor genes and their association with colon and rectal cancer development and prognosis. Int J Cancer J Inter du Cancer. 2012;130(12):2974–2980.
   PubMed Web of Science ®Google Scholar
• Messaritakis I, Stogiannitsi M, Koulouridi A, et al. Evaluation of the detection of Toll-like receptors (TLRs) in cancer development and progression in patients with colorectal cancer. PloS one. 2018;13:6.
   Web of Science ®Google Scholar
• Yesudhas D, Gosu V, Anwar MA, et al. Multiple Roles of Toll-Like Receptor 4 in Colorectal Cancer. Front Immunol. 2014;5:334.
   PubMed Web of Science ®Google Scholar
• Castro FA, Forsti A, Buch S, et al. TLR-3 polymorphism is an independent prognostic marker for stage II colorectal cancer. Eur j cancer. 2011;47(8):1203–1210. DOI:10.1016/j.ejca.2010.12.011
   PubMed Web of Science ®Google Scholar
• Shoeib SM, Mohamed WS, Nagy HM. Asp299Gly polymorphism in TLR4 gene in patients with colorectal cancer. Genet Mol Res. 2019;18:1.
   Google Scholar
• Xu C, Qiao Y, Zhang D. [Expression of Toll-like receptors in human hepatocellular carcinoma and its correlation with inflammasome-associated cytokines]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2017;33:1182–1186.
   PubMedGoogle Scholar
• Davoodi H, Seow HF. Variant Toll-like receptor4 (Asp299Gly and Thr399Ile alleles) and Toll-like receptor2 (Arg753Gln and Arg677Trp alleles) in colorectal cancer. Iran J Allergy Asthma Immunol. 2011;10(2):91–99.
   PubMed Web of Science ®Google Scholar
• Klimosch SN, Försti A, Eckert J, et al. Functional TLR5 genetic variants affect human colorectal cancer survival. Cancer Res. 2013;73(24):7232–7242. DOI:10.1158/0008-5472.CAN-13-1746
   PubMed Web of Science ®Google Scholar
• Okazaki S, Stintzing S, Heinemann V, et al. TLR6 polymorphism associated with overall survival in metastatic colorectal cancer (mCRC) patients treated with FOLFIRI/Bevacizumab enrolled in FIRE3. J Clin Oncol. 2015;33(15_suppl):11039–11039.
   Google Scholar
• Okazaki S, Stintzing S, Sunakawa Y, et al. Polymorphisms in toll-like receptor (TLR) genes in the prediction of outcome for cetuximab-based treatment in patients with metastatic colorectal cancer (mCRC). J Clin oncol. 2016;34(15):3588. DOI:10.1200/JCO.2016.34.15_suppl.3588
   PubMedGoogle Scholar
• Semlali A, Parine NR, Al Amri A, et al. Association between TLR-9 polymorphisms and colon cancer susceptibility in Saudi Arabian female patients. Onco Targets Ther. 2016;10:1–11.
   PubMed Web of Science ®Google Scholar
• Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–674.
   PubMed Web of Science ®Google Scholar
• Sato Y, Goto Y, Narita N, et al. Cancer cells expressing toll-like receptors and the tumor microenvironment. Cancer Microenviron. 2009;2(1):205–214.
   PubMedGoogle Scholar
• Ridnour LA, Cheng RY, Switzer CH, et al. Molecular pathways: toll-like receptors in the tumor microenvironment – poor prognosis or new therapeutic opportunity. Clin Cancer Res. 2013;19(6):1340–1346. DOI:10.1158/1078-0432.CCR-12-0408
   PubMed Web of Science ®Google Scholar
• Yu L, Wang L, Chen S. Dual character of toll-like receptor signaling: pro-tumorigenic effects and anti-tumor functions. Biochim Biophys Acta. 2013;1835(2):144–154.
   PubMed Web of Science ®Google Scholar
• Bednarczyk M, Muc-Wierzgoń M, Walkiewicz K, et al. Profile of gene expression of TLR-signaling pathways in colorectal cancer tissues. Int J Immunopathol Pharmacol. 2017;30(3):322–326. DOI:10.1177/0394632017716048
   PubMed Web of Science ®Google Scholar
• Lu CC, Kuo HC, Wang FS, et al. Upregulation of TLRs and IL-6 as a marker in human colorectal cancer. Int J Mol Sci. 2015;16(1):159–177.
   Web of Science ®Google Scholar
• Paarnio K, Vayrynen S, Klintrup K, et al. Divergent expression of bacterial wall sensing TLR2 and TLR4 in colorectal cancer. World J Gastroenterol. 2017;23:4831–4838.
   PubMed Web of Science ®Google Scholar
• Klimosch SN, Försti A, Eckert J, et al. TLR5 genetic variants affect human colorectal cancer survival. Cancer Res. 2013;73(24):7232–7242.
   PubMed Web of Science ®Google Scholar
• Grimm M, Kim M, Rosenwald A, et al. Toll-like receptor (TLR) 7 and TLR8 expression on CD133 + cells in colorectal cancer points to a specific role for inflammation-induced TLRs in tumourigenesis and tumour progression. Eur J Cancer. 2010;46(15):2849–2857. DOI:10.1016/j.ejca.2010.07.017
   PubMed Web of Science ®Google Scholar
• He L, Wang F, Tian H, et al. The expression profile of RNA sensors in colorectal cancer and its correlation with cancer stages. Transl Cancer Res. 2019;8(4):1351.
   Web of Science ®Google Scholar
• Pimentel-Nunes P, Teixeira AL, Pereira C, et al. Functional polymorphisms of Toll-like receptors 2 and 4 alter the risk for colorectal carcinoma in Europeans. Dig Liver Dis. 2013;45:63–69.
   PubMedGoogle Scholar
• Li TT, Ogino S, Qian ZR. Toll-like receptor signaling in colorectal cancer: carcinogenesis to cancer therapy. World J Gastroenterol. 2014;20(47):17699–17708.
   PubMed Web of Science ®Google Scholar
• Salcedo R, Worschech A, Cardone M, et al. MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18. J Exp Med. 2010;207:1625–1636.
   PubMed Web of Science ®Google Scholar
• Pradere JP, Dapito DH, Schwabe RF, et al. Yang of Toll-like receptors in cancer. Oncogene. 2014;33:3485–3495.
   PubMed Web of Science ®Google Scholar
• Lowe EL, Crother TR, Rabizadeh S, et al. Toll-like receptor 2 signaling protects mice from tumor development in a mouse model of colitis-induced cancer. PLoS One. 2010;5:e13027.
   PubMed Web of Science ®Google Scholar
• Paarnio K, Tuomisto A, Väyrynen SA, et al. Serum TLR2 and TLR4 levels in colorectal cancer and their association with systemic inflammatory markers, tumor characteristics, and disease outcome. Apmis. 2019;127(8):561–569.
   PubMed Web of Science ®Google Scholar
• EL W, Qian ZR, Nakasono M, et al. High expression of Toll-like receptor 4/myeloid differentiation factor 88 signals correlates with poor prognosis in colorectal cancer. Br J Cancer. 2010;102:908–915. DOI:10.1038/sj.bjc.6605558
   PubMed Web of Science ®Google Scholar
• Eiro N, Gonzalez L, Gonzalez LO, et al. Toll-like receptor-4 expression by stromal fibroblasts is associated with poor prognosis in colorectal cancer. J Immunother. 2013;36(6):342–349. DOI:10.1097/CJI.0b013e31829d85e6
   PubMed Web of Science ®Google Scholar
• Luddy KA, Robertson-Tessi M, Tafreshi NK, et al. The role of toll-like receptors in colorectal cancer progression: evidence for epithelial to leucocytic transition. Front Immunol. 2014;5:429.
   PubMed Web of Science ®Google Scholar
• Tye H, Jenkins BJ. Tying the knot between cytokine and toll-like receptor signaling in gastrointestinal tract cancers. Cancer Sci. 2013;104:1139–1145.
   PubMed Web of Science ®Google Scholar
• Xu H, Wu Q, Dang S, et al. Alteration of CXCR7 expression mediated by TLR4 promotes tumor cell proliferation and migration in human colorectal carcinoma. PLoS One. 2011;6:e27399.
   PubMed Web of Science ®Google Scholar
• So EY, Ouchi T. The application of Toll like receptors for cancer therapy. Int J Biol Sci. 2010;6:675–681.
   PubMed Web of Science ®Google Scholar
• Rhee SH, Im E, Pothoulakis C. Toll-like receptor 5 engagement modulates tumor development and growth in a mouse xenograft model of human colon cancer. Gastroenterology. 2008;135(2):518–528.
   PubMed Web of Science ®Google Scholar
• Fűri I, Sipos F, Germann TM, et al. Epithelial toll-like receptor 9 signaling in colorectal inflammation and cancer: clinico-pathogenic aspects. World J Gastroenterol. 2013;19:4119–4126.
   PubMed Web of Science ®Google Scholar
• Gao C, Qiao T, Zhang B, et al. TLR9 signaling activation at different stages in colorectal cancer and NF-kappaB expression. Onco Targets Ther. 2018;11:5963–5971.
   PubMed Web of Science ®Google Scholar
• Kouzarides T. Chromatin modifications and their function. Cell. 2007;128(4):693–705.
   PubMed Web of Science ®Google Scholar
• Baretti M, Azad NS. The role of epigenetic therapies in colorectal cancer. Curr Probl Cancer. 2018;42:530–547.
   PubMed Web of Science ®Google Scholar
• Plass C, Pfister SM, Lindroth AM, et al. Mutations in regulators of the epigenome and their connections to global chromatin patterns in cancer. Nat Rev Genet. 2013;14(11):765–780. DOI:10.1038/nrg3554
   PubMed Web of Science ®Google Scholar
• Suva ML, Riggi N, Bernstein BE. Riggi N and Bernstein BE. Epigenetic reprogramming in cancer. Science. 2013;339(6127):1567–1570.
   PubMed Web of Science ®Google Scholar
• Lao VV, Grady WM. Epigenetics and colorectal cancer. Nat Rev Gastroenterol Hepatol. 2011;;8:686–700.
   PubMed Web of Science ®Google Scholar
• Dhir M, Yachida S, Neste LV, et al. Sessile serrated adenomas and classical adenomas: an epigenetic perspective on premalignant neoplastic lesions of the gastrointestinal tract. Int J Cancer. 2011;129(8):1889–1898. DOI:10.1002/ijc.25847
   PubMed Web of Science ®Google Scholar
• Guo H, Chen Y, Hu X, et al. “The regulation of toll-like receptor 2 by miR-143 suppresses the invasion and migration of a subset of human colorectal carcinoma cells. Mol Cancer. 2013;12:77. DOI:10.1186/1476-4598-12-77
   PubMed Web of Science ®Google Scholar
• He X, Jing Z, Cheng G. MicroRNAs: new regulators of Toll-like receptor signalling pathways. Biomed Res Int. 2014;2014:1–14.
   Web of Science ®Google Scholar
• Liu G, Friggeri A, Yang Y, et al. miR-147, a microRNA that is induced upon Toll-like receptor stimulation, regulates murine macrophage inflammatory responses. Proc Natl Acad Sci USA. 2009;106:15819–15824.
   PubMed Web of Science ®Google Scholar
• Proenca MA, Biselli JM, Succi M, et al. Relationship between fusobacterium nucleatum, inflammatory mediators and microRNAs in colorectal carcinogenesis. World J Gastroenterol. 2018;24:5351–5365.
   PubMed Web of Science ®Google Scholar
• Temraz S, Nassar F, Nasr R, et al. Biomarker for Immunotherapy in Colorectal Cancer. Int J Mol Sci. 2019;20(17):4155.
   PubMed Web of Science ®Google Scholar
• Johnnidis JB, Harris MH, Wheeler RT, et al. “Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. Nature. 2008;451(7182):1125–1129. DOI:10.1038/nature06607
   PubMed Web of Science ®Google Scholar
• Jiang C, Zhu W, Xu J, et al. MicroRNA-26a negatively regulates toll-like receptor 3 expression of rat macrophages and ameliorates pristane induced arthritis in rats, . Arthritis Res Ther. 2014;16(1):R9. DOI:10.1186/ar4435
   PubMed Web of Science ®Google Scholar
• Raisch J, Darfeuille-Michaud A, Nguyen HTT. Role of microRNAs in the immune system, inflammation and cancer. World J Gastroenterol. 2013;19(20):2985.
   PubMed Web of Science ®Google Scholar
• Takahashi K, Sugi Y, Hosono A, et al. Epigenetic regulation of TLR4 gene expression in intestinal epithelial cells for the maintenance of intestinal homeostasis. J Immunol. 2009;183(10):6522–6529.
   PubMed Web of Science ®Google Scholar
• Dong H, Wang W, Mo S, et al. SP1-induced lncRNA AGAP2-AS1 expression promotes chemoresistance of breast cancer by epigenetic regulation of MyD88. J Exp Clin Cancer Res. 2018;37:202.
   PubMed Web of Science ®Google Scholar
• Androulidaki A, Iliopoulos D, Arranz A, et al. The kinase Akt1 controls macrophage response to lipopolysaccharide by regulating MicroRNAs, . Immunity. 2009;31(2):220–231. DOI:10.1016/j.immuni.2009.06.024
   PubMed Web of Science ®Google Scholar
• Tserel L, Runnel T, Kisand K, et al. MicroRNA expression profiles of human blood monocyte-derived dendritic cells and macrophages reveal miR-511 as putative positive regulator of toll-like receptor 4, . J Biol Chem. 2011;286(30):26487–26495. DOI:10.1074/jbc.M110.213561
   PubMed Web of Science ®Google Scholar
• Lai L, Song Y, Liu Y, et al. MicroRNA-92a negatively regulates Toll-like receptor (TLR)-triggered inflammatory response in macrophages by targeting MKK4 kinase. J Biol Chem. 2013;288(11):7956–7967.
   PubMed Web of Science ®Google Scholar
• El Bairi K, Tariq K, Himri I, et al. Decoding colorectal cancer epigenomics. Cancer Genet. 2018;220:49–76.
   PubMed Web of Science ®Google Scholar
• Ma C, Li Y, Li M, et al. MicroRNA-124 negatively regulates TLR signaling in alveolar macrophages in response to mycobacterial infection. Mol Immunol. 2014;62:150–158.
   PubMed Web of Science ®Google Scholar
• Arenas-Padilla M, Mata-Haro V. Regulation of TLR signaling pathways by microRNAs: implications in inflammatory diseases. Cent Eur J Immunol. 2018;43(4):482–489.
   PubMed Web of Science ®Google Scholar
• Wang HF, Li Y, Wang YQ, et al. MicroRNA-494-3p alleviates inflammatory response in sepsis by targeting TLR6. Eur Rev Med Pharmacol Sci. 2019;23(7):2971–2977.
   PubMed Web of Science ®Google Scholar
• Yu L, Wang L, Chen S. Exogenous or endogenous Toll-like receptor ligands: which is the MVP in tumorigenesis? Cell Mol Life Sci. 2012;69(6):935–949.
   PubMed Web of Science ®Google Scholar
• Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Front Immunol. 2014;5:461.
   PubMed Web of Science ®Google Scholar
• Tanaka T. Development of an inflammation-associated colorectal cancer model and its application for research on carcinogenesis and chemoprevention. Int J Inflam. 2012;2012:1–16.
   PubMedGoogle Scholar
• Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on toll-like receptors. Nat Immunol. 2010;11:373–384.
   PubMed Web of Science ®Google Scholar
• Blasius AL, Beutler B. Intracellular toll-like receptors. Immunity. 2010;32:305–315.
   PubMed Web of Science ®Google Scholar
• Yu L, Wang L, Chen S. Endogenous toll-like receptor ligands and their biological significance. J Cell Mol Med. 2010;14(11):2592–2603.
   PubMed Web of Science ®Google Scholar
• Takeuchi O, Sato S, Horiuchi T, et al. Cutting edge: role of toll-like receptor 1 in mediating immune response to microbial lipoproteins. J Immunol. 2002;169(1):10–410. DOI:10.4049/jimmunol.169.1.10
   PubMed Web of Science ®Google Scholar
• Takeuchi O, Kaufmann A, Grote K, et al. Cutting edge: preferentially the R-stereoisomer of the mycoplasmal lipopeptide macrophage-activating lipopeptide-2 activates immune cells through a toll-like receptor 2- and MyD88-dependent signaling pathway. J Immunol. 2000;164(2):554–710. DOI:10.4049/jimmunol.164.2.554
   PubMed Web of Science ®Google Scholar
• Vabulas RM, Ahmad-Nejad P, da Costa C, et al. HSP60s use toll-like receptor 2 (TLR2) and TLR4 to activate the toll/interleukin-1 receptor signaling pathway in innate immune cells. J Biol Chem. 2001;276:31332–31339.
   PubMed Web of Science ®Google Scholar
• Asea A, Rehli M, Kabingu E, et al. Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J Biol Chem. 2002;277:15028–15034.
   PubMed Web of Science ®Google Scholar
• Lee MJ, Lee JK, Choi JW, et al. Interleukin-6 induces S100A9 expression in colonic epithelial cells through STAT3 activation in experimental ulcerative colitis. PLoS One. 2012;7:e38801.
   PubMed Web of Science ®Google Scholar
• Tian J, Avalos AM, Mao SY, et al. Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nat Immunol. 2007;8:487–496.
   PubMed Web of Science ®Google Scholar
• Imai Y, Kuba K, Neely GG, et al. Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell. 2008;133:235–249.
   PubMed Web of Science ®Google Scholar
• Hayashi F, Smith KD, Ozinsky A, et al. The innate immune response to bacterial flagellin is mediated by toll-like receptor 5. Nature. 2001;410(6832):1099–10310. DOI:10.1038/35074106
   PubMed Web of Science ®Google Scholar
• Takeuchi O, Kawai T, Muhlradt PF, et al. Discrimination of bacterial lipoproteins by toll-like receptor 6. Int Immunol. 2001;13(7):933–4010. DOI:10.1093/intimm/13.7.933
   PubMed Web of Science ®Google Scholar
• Alexopoulou L, Holt AC, Medzhitov R, et al. Recognition of double-stranded RNA and activation of NF-kappaB by toll-like receptor 3. Nature. 2001;413(6857):732–810.
   PubMed Web of Science ®Google Scholar
• Kariko K, Ni H, Capodici J, et al. mRNA is an endogenous ligand for Toll-like receptor 3. J Biol Chem. 2004;279:12542–12550.
   PubMed Web of Science ®Google Scholar
• Heil F, Hemmi H, Hochrein H, et al. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science. 2004;303(5663):1526–1910. DOI:10.1126/science.1093620
   PubMed Web of Science ®Google Scholar
• Sioud M. Induction of inflammatory cytokines and interferon responses by double-stranded and single-stranded siRNAs is sequence-dependent and requires endosomal localization. J Mol Biol. 2005;348:1079–1090.
   PubMed Web of Science ®Google Scholar
• Zhang P, Cox CJ, Alvarez KM, et al. Cutting edge: cardiac myosin activates innate immune responses through TLRs. J Immunol. 2009;183:27–31.
   PubMed Web of Science ®Google Scholar
• Hemmi H, Takeuchi O, Kawai T, et al. A toll-like receptor recognizes bacterial DNA. Nature. 2000;408(6813):510–740. DOI:10.1038/35047123
   PubMed Web of Science ®Google Scholar
• Krug A, French AR, Barchet W, et al. TLR9-dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function. Immunity. 2004;21(1):107–1910. DOI:10.1016/j.immuni.2004.06.007
   PubMed Web of Science ®Google Scholar
• Eiring AM, Harb JG, Neviani P, et al. miR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blasts. Cell. 2010;140:652–665.
   PubMed Web of Science ®Google Scholar
• Fabbri M. TLRs as miRNA receptors. Cancer Res. 2012;72(24):6333–6337. DOI:10.1158/0008-5472.CAN-12-3229
   PubMed Web of Science ®Google Scholar
• Fabbri M, Paone A, Calore F, et al. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci USA. 2012;109:E2110–6.
   PubMed Web of Science ®Google Scholar
• Curtale G, Rubino M, Locati M. MicroRNAs as molecular switches in macrophage activation. Front Immunol. 2019;10:799.
   PubMed Web of Science ®Google Scholar
• Xie Z, Huang G, Wang Z, et al. Epigenetic regulation of Toll-like receptors and its roles in type 1 diabetes. J Mol Med. 2018;96(8):741–775.
   Web of Science ®Google Scholar
• Kreidieh M, Mukherji D, Temraz S, et al. Expanding the scope of immunotherapy in colorectal cancer: current clinical approaches and future directions. Biomed Res Int. 2020;2020:1–24.
   PubMed Web of Science ®Google Scholar
• Reed DZ, Krupp N, Suman S, et al. An evaluation of innate immune anomalies in colorectal tumorigenesis and precision medicine. J Cancer Sci Ther. 2019;11:213–223.
   Google Scholar
• Kaczanowska S, Joseph AM, Davila E. TLR agonists: our best frenemy in cancer immunotherapy. J Leukoc Biol. 2013;93(6):847–863.
   PubMed Web of Science ®Google Scholar
• Moradi‐Marjaneh R, Hassanian SM, Fiuji H, et al. Toll like receptor signaling pathway as a potential therapeutic target in colorectal cancer. J Cell Physiol. 2018;233(8):5613–5622.
   PubMed Web of Science ®Google Scholar
• Jin B, Sun T, Yu XH, et al. The effects of TLR activation on T-cell development and differentiation, . Clin Dev Immunol. 2012;2012:Article ID 836485, 32 pages.
   Google Scholar
• Connolly DJ, O’Neill LA. New developments in Toll-like receptor targeted therapeutics. Curr Opin Pharmacol. 2012;12(4):510–518.
   PubMed Web of Science ®Google Scholar
• Rammensee HG, Wiesmüller KH, Chandran PA, et al. A new synthetic toll-like receptor 1/2 ligand is an efficient adjuvant for peptide vaccination in a human volunteer. J Immunother Cancer. 2019;7(1):307.
   PubMed Web of Science ®Google Scholar
• Yuk JM, Shin DM, Song KS, et al. Bacillus calmette-guerin cell wall cytoskeleton enhances colon cancer radiosensitivity through autophagy. Autophagy. 2010;6(1):46–60.
   PubMed Web of Science ®Google Scholar
• Uyl-deGroot C, Vermorken J, Hanna M, et al. Immunotherapy with autologous tumor cellBCG vaccine in patients with colon cancer: a prospective study of medical and economic benefits. Vaccine. 2005;23(17):2379–2387.
   PubMed Web of Science ®Google Scholar
• Isambert N, Fumoleau P, Paul C, et al. Phase I study of OM-174, a lipid A analogue, with assessment of immunological response, in patients with refractorysolid tumors. BMC Cancer. 2013;13(1):172.
   PubMedGoogle Scholar
• Galluzzi L, Vacchelli E, Eggermont A, et al. Trial watch: experimental Toll-like receptor agonists for cancer therapy. Oncoimmunology. 2012;1(5):699–739.
   PubMed Web of Science ®Google Scholar
• Lynch D, Murphy A. The emerging role of immunotherapy in colorectal cancer. Ann Transl Med. 2016;4:16.
   PubMed Web of Science ®Google Scholar
• Lai Y, Weng J, Wei X, et al. Toll-like receptor 2 costimulation potentiates the antitumor efficacy of CAR T cells. Leukemia. 2018;32(3):801–808.
   PubMed Web of Science ®Google Scholar
• Neidhart J, Allen KO, Barlow DL, et al. Immunization of colorectal cancer patients with recombinant baculovirus-derived KSA (Ep-CAM) formulated with monophosphoryl lipid A in liposomal emulsion, with and without granulocyte-macrophage colony-stimulating factor. Vaccine. 2004;22(5):773–780.
   PubMed Web of Science ®Google Scholar
• Stier S, Maletzki C, Klier U, et al. Combinations of TLR ligands: a promising approach in cancer immunotherapy. Clin Dev Immunol. 2013;2013:1–14.
   PubMedGoogle Scholar
• Butts C, Murray N, Maksymiuk A, et al. Randomized phase IIB trial of BLP25 liposome vaccine in stage IIIB and IV non-small-cell lung cancer. J Clin Oncol. 2005;23(27):6674–8110. DOI:10.1200/JCO.2005.13.011
   PubMed Web of Science ®Google Scholar
• Kroemer G, Zitvogel L, Galluzzi L. Victories and deceptions in tumor immunology: Stimuvax. Oncoimmunology. 2013;2(1):e23687.
   PubMed Web of Science ®Google Scholar
• Kesselring R, Glaesner J, Hiergeist A, et al. expression in tumor cells supports colorectal cancer progression through reduction of antimicrobial defense and stabilization of STAT3. Cancer cell. 2016;29(5):684–696.
   PubMed Web of Science ®Google Scholar
• Jeung HC, Moon Y, Rha S, et al. III trial of adjuvant 5-fluorouracil and adriamycin versus 5-fluorouracil, adriamycin, and polyadenylic–polyuridylic acid (poly A: U) for locally advanced gastric cancer after curative surgery: Final results of 15-year follow-up. Ann Oncol. 2007;19(3):520–526.
   PubMed Web of Science ®Google Scholar
• Taura M, Fukuda R, Suico MA, et al. TLR3 induction by anticancer drugs potentiates poly I: C-induced tumor cell apoptosis. Cancer Sci. 2010;101(7):1610–1617.
   PubMed Web of Science ®Google Scholar
• Zheng JH, Nguyen VH, Jiang SN, et al. Two-step enhanced cancer immunotherapy with engineered Salmonella typhimurium secreting heterologous flagellin. Sci Transl Med. 2017;9(376):eaak9.
   Web of Science ®Google Scholar
• Ito H, Ando T, Arioka Y, et al. Inhibition of indoleamine. 2, 3-dioxygenase activity enhances the anti-tumour effects of a Toll-like receptor 7 agonists in an established cancer model. Immunology. 2015;144(4):621–630.
   PubMed Web of Science ®Google Scholar
• Dumitru CD, Antonysamy MA, Tomai MA, et al. Potentiation of the antitumor effects of imidazoquinoline immune response modifiers by cyclophosphamide. Cancer Biol Ther. 2010;10(2):155–165.
   PubMed Web of Science ®Google Scholar
• Adlard AL, Dovedi SJ, Telfer BA, et al. A novel systemically administered toll-like receptor 7 agonist potentiates the effect of ionizing radiation in murine solid tumor models. Int J Cancer. 2014;135(4):820–829.
   PubMed Web of Science ®Google Scholar
• Ikeguchi M, Arai Y, Maeta Y, et al. Topoisomerase i expression in tumors as a biological marker for CPT-11 chemosensitivity in patients with colorectal cancer, . Surg Today. 2011;41(9):1196–1199.
   PubMed Web of Science ®Google Scholar
• Jahrsdörfer B, Weiner GJ. CpG oligodeoxynucleotides as immunotherapy in cancer. Update Cancer Therapeutics. 2008;3(1):27–32. DOi:10.1016/j.uct.2007.11.003
   PubMedGoogle Scholar
• Murad YM, Clay TM, Lyerly HK, et al. CPG-7909 (PF-3512676, ProMune®): Toll-like receptor-9 agonist in cancer therapy. Expert Opin Biol Ther. 2007;7(8):1257–1266.
   PubMed Web of Science ®Google Scholar
• Kim IY, Yan X, Tohme S, et al. Toll like receptor (TLR)-9 agonist, inhibits metastatic colon adenocarcinoma in a murine hepatic tumor model. J Surg Res. 2012;174(2):284–290.
   PubMed Web of Science ®Google Scholar
• Wang S, Campos J, Gallotta M, et al. Intratumoral injection of a CpG oligonucleotide reverts resistance to PD-1 blockade by expanding multifunctional CD8+ T cells. Proc Nat Acad Sci. 2016;113(46):7240–7249.
   Web of Science ®Google Scholar
• Dong T, Yi T, Yang M, et al. Cooperation of α-galactosylceramide-loaded tumour cells and TLR9 agonists induce potent anti-tumour responses in a murine colon cancer model. Biochem J. 2016;473(1):7–19.
   PubMedGoogle Scholar
• Ray A, Tian Z, Das DS, et al. A novel TLR-9 agonist C792 inhibits plasmacytoid dendritic cell-induced myeloma cell growth and enhance cytotoxicity of bortezomib. Leukemia. 2014;28(8):1716–1724.
   PubMed Web of Science ®Google Scholar
• Chen GY, Chen CL, Tuan HY, et al. Graphene oxide triggers Toll-Like receptors/autophagy responses in vitro and inhibits tumor growth In vivo. Adv Healthc Mater. 2014;3(9):1486–1495.
   PubMed Web of Science ®Google Scholar
• Park GB, Kim D. TLR-mediated miR-125b-5p downregulation enhances CD248-induced metastasis and drug resistance in colorectal cancer cells. 2019. DOI:10.21203/rs.2.10556/v1
   Google Scholar
• Ye K, Wu Y, Sun Y, et al. TLR4 siRNA inhibits proliferation and invasion in colorectal cancer cells by downregulating ACAT1 expression. Life Sci. 2016;155:133–139.
   PubMed Web of Science ®Google Scholar
• Pagliuca A, Valvo C, Fabrizi E, et al. Analysis of the combined action of miR-143 and miR-145 on oncogenic pathways in colorectal cancer cells reveals a coordinate program of gene repression. Oncogene. 2013;32:4806–4813. https://doi.org/10.1038/onc.2012.495.
   Web of Science ®Google Scholar
• Yang H, Zhou H, Feng P, et al. Reduced expression of Toll-like receptor 4 inhibits human breast cancer cells proliferation and inflammatory cytokines secretion. J Exp Clin Cancer Res. 2010;29(1):92.
   PubMedGoogle Scholar
• Liu Y, Li T, Xu Y, et al. Effects of TLR4 gene silencing on the proliferation and apotosis of hepatocarcinoma HEPG2 cells. Oncol Lett. 2016;11(5):3054–3060.
   PubMed Web of Science ®Google Scholar
• Schary Y, Naftali-Shani N, Leor J. CRISPR/Cas9-Based Knockout of the TLR4 gene Enhances Secretion of Extracellular Vesicles WithAnti-Inflammatory Properties From Human Cardiac Mesenchymal Stromal Cells. Circ Res. 2019;125(1):A719–A719.
   Google Scholar
• Serrano R, Wesch D, Kabelitz D. Activation of Human γδ T Cells: Modulation by Toll-Like Receptor 8 Ligands and Role of Monocytes. Cells. 2020;9(3):713.
   Web of Science ®Google Scholar