The Yin and Yang of Toll-like Receptors in Cancer

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2013 Aug 13

PMID 23934186

Citations 151

Authors

J-P Pradere

D H Dapito

R F Schwabe

Affiliations

Soon will be listed here.

Abstract

Recognition of non-self molecular patterns by pattern recognition receptors is a cornerstone of innate immunity. Toll-like receptors (TLRs) exert a key role in recognizing pathogen-associated molecular patterns (PAMPs) but have also been implicated in the recognition of damage-associated molecular patterns (DAMPs). As such, TLRs regulate a wide range of biological responses including inflammatory and immune responses during carcinogenesis. The high expression of TLRs by antigen-presenting cells, including dendritic cells, and their ability to induce antitumor mediators such as type I interferon has led to efforts to utilize TLR agonists in tumor therapy in order to convert the often tolerant immune response toward antitumor responses. However, TLRs are also increasingly recognized as regulators of tumor-promoting inflammation and promoters of tumor survival signals. Here, we will review in detail the dichotomous role of TLRs in tumor biology, focusing on relevant TLR-dependent pro- and antitumor pathways, and discuss clinical applications of TLR-targeted therapies for tumor prevention and treatment.

Citing Articles

Poly(I:C) signaling induces robust CXCL10 production and apoptosis in human esophageal squamous cell carcinoma cells.

Sato Y, Yamaya A, Sonoda K, Wakita A, Nagaki Y, Sasamori R Hum Cell. 2025; 38(3):63.

PMID: 40029556 PMC: 11876272. DOI: 10.1007/s13577-025-01191-1.

Mizhuo Guanchangye enema delays the decline of renal function in rats with chronic kidney disease by intervening in the TLR4/MyD88/NF-κB pathway.

Li H, Xu P, Zhang X, Ye N, Xu F, Liang B Front Med (Lausanne). 2024; 11:1454506.

PMID: 39529796 PMC: 11550938. DOI: 10.3389/fmed.2024.1454506.

New Insights into the Pleiotropic Actions of Dipeptidyl Peptidase-4 Inhibitors Beyond Glycaemic Control.

Mangoura S, Ahmed M, Zaka A touchREV Endocrinol. 2024; 20(2):19-29.

PMID: 39526061 PMC: 11548370. DOI: 10.17925/EE.2024.20.2.5.

Machine learning-derived peripheral blood transcriptomic biomarkers for early lung cancer diagnosis: Unveiling tumor-immune interaction mechanisms.

Li X, Li X, Qin J, Lei L, Guo H, Zheng X Biofactors. 2024; 51(1):e2129.

PMID: 39415336 PMC: 11681315. DOI: 10.1002/biof.2129.

Clinicopathological Significance and Prognostic Role of High Mobility Group Box 1 (HMGB1), Toll-Like Receptor (TLR) 2 and TLR4 in Breast Cancer.

Taguchi R, Yamaguchi-Tanaka M, Takagi K, Sato A, Miki Y, Miyashita M Acta Histochem Cytochem. 2024; 57(2):75-83.

PMID: 38695037 PMC: 11058461. DOI: 10.1267/ahc.24-00006.

References

Xiao H, Gulen M, Qin J, Yao J, Bulek K, Kish D . The Toll-interleukin-1 receptor member SIGIRR regulates colonic epithelial homeostasis, inflammation, and tumorigenesis. Immunity. 2007; 26(4):461-75. DOI: 10.1016/j.immuni.2007.02.012. View

de Palma M, Mazzieri R, Politi L, Pucci F, Zonari E, Sitia G . Tumor-targeted interferon-alpha delivery by Tie2-expressing monocytes inhibits tumor growth and metastasis. Cancer Cell. 2008; 14(4):299-311. DOI: 10.1016/j.ccr.2008.09.004. View

Smits E, Ponsaerts P, Berneman Z, Van Tendeloo V . The use of TLR7 and TLR8 ligands for the enhancement of cancer immunotherapy. Oncologist. 2008; 13(8):859-75. DOI: 10.1634/theoncologist.2008-0097. View

Rossignol D, Lynn M . Antagonism of in vivo and ex vivo response to endotoxin by E5564, a synthetic lipid A analogue. J Endotoxin Res. 2003; 8(6):483-8. DOI: 10.1179/096805102125001127. View

Fukata M, Shang L, Santaolalla R, Sotolongo J, Pastorini C, Espana C . Constitutive activation of epithelial TLR4 augments inflammatory responses to mucosal injury and drives colitis-associated tumorigenesis. Inflamm Bowel Dis. 2011; 17(7):1464-73. PMC: 3117047. DOI: 10.1002/ibd.21527. View

Babjuk M, Oosterlinck W, Sylvester R, Kaasinen E, Bohle A, Palou-Redorta J . EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update. Eur Urol. 2011; 59(6):997-1008. DOI: 10.1016/j.eururo.2011.03.017. View

Kutikhin A . Impact of Toll-like receptor 4 polymorphisms on risk of cancer. Hum Immunol. 2010; 72(2):193-206. DOI: 10.1016/j.humimm.2010.11.003. View

Fiebiger E, Maurer D, Holub H, Reininger B, Hartmann G, Woisetschlager M . Serum IgG autoantibodies directed against the alpha chain of Fc epsilon RI: a selective marker and pathogenetic factor for a distinct subset of chronic urticaria patients?. J Clin Invest. 1995; 96(6):2606-12. PMC: 185965. DOI: 10.1172/JCI118325. View

Kolida S, Gibson G . Synbiotics in health and disease. Annu Rev Food Sci Technol. 2011; 2:373-93. DOI: 10.1146/annurev-food-022510-133739. View

10.

Schreiber R, Old L, Smyth M . Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science. 2011; 331(6024):1565-70. DOI: 10.1126/science.1203486. View

11.

Cornell R, Liljequist B, Bartizal K . Depressed liver regeneration after partial hepatectomy of germ-free, athymic and lipopolysaccharide-resistant mice. Hepatology. 1990; 11(6):916-22. DOI: 10.1002/hep.1840110603. View

12.

Yusuf N, Nasti T, Long J, Naseemuddin M, Lucas A, Xu H . Protective role of Toll-like receptor 4 during the initiation stage of cutaneous chemical carcinogenesis. Cancer Res. 2008; 68(2):615-22. PMC: 3568948. DOI: 10.1158/0008-5472.CAN-07-5219. View

13.

Mittal D, Saccheri F, Venereau E, Pusterla T, Bianchi M, Rescigno M . TLR4-mediated skin carcinogenesis is dependent on immune and radioresistant cells. EMBO J. 2010; 29(13):2242-52. PMC: 2905255. DOI: 10.1038/emboj.2010.94. View

14.

Ochi A, Nguyen A, Bedrosian A, Mushlin H, Zarbakhsh S, Barilla R . MyD88 inhibition amplifies dendritic cell capacity to promote pancreatic carcinogenesis via Th2 cells. J Exp Med. 2012; 209(9):1671-87. PMC: 3428946. DOI: 10.1084/jem.20111706. View

15.

Geisse J, Caro I, Lindholm J, Golitz L, Stampone P, Owens M . Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from two phase III, randomized, vehicle-controlled studies. J Am Acad Dermatol. 2004; 50(5):722-33. DOI: 10.1016/j.jaad.2003.11.066. View

16.

Ren T, Xu L, Jiao S, Wang Y, Cai Y, Liang Y . TLR9 signaling promotes tumor progression of human lung cancer cell in vivo. Pathol Oncol Res. 2009; 15(4):623-30. DOI: 10.1007/s12253-009-9162-0. View

17.

Baines J, Celis E . Immune-mediated tumor regression induced by CpG-containing oligodeoxynucleotides. Clin Cancer Res. 2003; 9(7):2693-700. View

18.

Srivastava K, Srivastava A, Kumar A, Mittal B . Significant association between toll-like receptor gene polymorphisms and gallbladder cancer. Liver Int. 2010; 30(7):1067-72. DOI: 10.1111/j.1478-3231.2010.02268.x. View

19.

Krieg A . Development of TLR9 agonists for cancer therapy. J Clin Invest. 2007; 117(5):1184-94. PMC: 1857270. DOI: 10.1172/JCI31414. View

20.

Stary G, Bangert C, Tauber M, Strohal R, Kopp T, Stingl G . Tumoricidal activity of TLR7/8-activated inflammatory dendritic cells. J Exp Med. 2007; 204(6):1441-51. PMC: 2118597. DOI: 10.1084/jem.20070021. View