• This record comes from PubMed

Toll-Like Receptor 3 in Solid Cancer and Therapy Resistance

. 2020 Nov 02 ; 12 (11) : . [epub] 20201102

Status PubMed-not-MEDLINE Language English Country Switzerland Media electronic

Document type Journal Article, Review

Grant support
17-28518A Agentura Pro Zdravotnický Výzkum České Republiky
LQ1605 Ministerstvo Školství, Mládeže a Tělovýchovy
ENOCH No. CZ.02.1.01/0.0/0.0/16_019/0000868 Ministerstvo Školství, Mládeže a Tělovýchovy

Toll-like receptor 3 (TLR3) is a member of the TLR family, which has been extensively studied for its antiviral function. It is highly expressed in the endosomes of antigen-presenting immune cells and epithelial cells. TLR3 binds specifically double-strand RNAs (dsRNAs), leading to the activation of mainly two downstream pathways: the phosphorylation of IRF3, with subsequent production of type I interferon, and the activation of NF-κB, which drives the production of inflammatory cytokines and chemokines. Several studies have demonstrated TLR3 expression in multiple neoplasia types including breast, prostate, and lung cancer. Most studies were focused on the beneficial role of TLR3 activation in tumor cells, which leads to the production of cytotoxic cytokines and interferons and promotes caspase-dependent apoptosis. Indeed, ligands of this receptor were proposed for the treatment of cancer, also in combination with conventional chemotherapy. In contrast to these findings, recent evidence showed a link between TLR3 and tumor progression, metastasis, and therapy resistance. In the present review, we summarize the current knowledge of the mechanisms through which TLR3 can either lead to tumor regression or promote carcinogenesis as well as the potential of TLR-based therapies in resistant cancer.

See more in PubMed

Blasius A.L., Beutler B. Intracellular Toll-like Receptors. Immunity. 2010;32:305–315. doi: 10.1016/j.immuni.2010.03.012. PubMed DOI

Choe J., Kelker M.S., Wilson I.A. Crystal structure of human toll-like receptor 3 (TLR3) ectodomain. Science. 2005;309:581–585. doi: 10.1126/science.1115253. PubMed DOI

Leonard J.N., Ghirlando R., Askins J., Bell J.K., Margulies D.H., Davies D.R., Segal D.M. The TLR3 signaling complex forms by cooperative receptor dimerization. Proc. Natl. Acad. Sci. USA. 2008;105:258–263. doi: 10.1073/pnas.0710779105. PubMed DOI PMC

De Bouteiller O., Merck E., Hasan U.A., Hubac S., Benguigui B., Trinchieri G., Bates E.E., Caux C. Recognition of double-stranded RNA by human toll-like receptor 3 and downstream receptor signaling requires multimerization and an acidic pH. J. Biol. Chem. 2005;280:38133–38145. doi: 10.1074/jbc.M507163200. PubMed DOI

Akira S., Uematsu S., Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124:783–801. doi: 10.1016/j.cell.2006.02.015. PubMed DOI

Oshiumi H., Matsumoto M., Funami K., Akazawa T., Seya T. TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-β induction. Nat. Immunol. 2003;4:161–167. doi: 10.1038/ni886. PubMed DOI

Yamamoto M., Sato S., Hemmi H., Hoshino K., Kaisho T., Sanjo H., Takeuchi O., Sugiyama M., Okabe M., Takeda K., et al. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science. 2003;301:640–643. doi: 10.1126/science.1087262. PubMed DOI

Sarkar S.N., Peters K.L., Elco C.P., Sakamoto S., Pal S., Sen G.C. Novel roles of TLR3 tyrosine phosphorylation and PI3 kinase in double-stranded RNA signaling. Nat. Struct. Mol. Biol. 2004;11:1060–1067. doi: 10.1038/nsmb847. PubMed DOI

Fitzgerald K.A., McWhirter S.M., Faia K.L., Rowe D.C., Latz E., Golenbock D.T., Coyle A.J., Liao S.M., Maniatis T. IKKepsilon and TBK1 are essential components of the IRF3 signalling pathway. Nat. Immunol. 2003;4:491–496. doi: 10.1038/ni921. PubMed DOI

Jiang Z., Mak T.W., Sen G., Li X. Toll-like receptor 3-mediated activation of NF-κB and IRF3 diverges at Toll-IL-1 receptor domain-containing adapter inducing IFN-β. Proc. Natl. Acad. Sci. USA. 2004;101:3533–3538. doi: 10.1073/pnas.0308496101. PubMed DOI PMC

Matsumoto M., Seya T. TLR3: Interferon induction by double-stranded RNA including poly(I:C) Adv. Drug Deliv. Rev. 2008;60:805–812. doi: 10.1016/j.addr.2007.11.005. PubMed DOI

Sivori S., Carlomagno S., Pesce S., Moretta A., Vitale M., Marcenaro E. TLR/NCR/KIR: Which one to use and when? Front. Immunol. 2014;5:1–10. doi: 10.3389/fimmu.2014.00105. PubMed DOI PMC

Town T., Jeng D., Alexopoulou L., Tan J., Flavell R.A. Microglia Recognize Double-Stranded RNA via TLR3. J. Immunol. 2006;176:3804–3812. doi: 10.4049/jimmunol.176.6.3804. PubMed DOI

Cameron J.S., Alexopoulou L., Sloane J.A., DiBernardo A.B., Ma Y., Kosaras B., Flavell R., Strittmatter S.M., Volpe J., Sidman R., et al. Toll-Like Receptor 3 Is a Potent Negative Regulator of Axonal Growth in Mammals. J. Neurosci. 2007;27:13033–13041. doi: 10.1523/JNEUROSCI.4290-06.2007. PubMed DOI PMC

Matsumoto M., Funami K., Tanabe M., Oshiumi H., Shingai M., Seto Y., Yamamoto A., Seya T. Subcellular Localization of Toll-Like Receptor 3 in Human Dendritic Cells. J. Immunol. 2003;171:3154–3162. doi: 10.4049/jimmunol.171.6.3154. PubMed DOI

Matsumoto M., Kikkawa S., Kohase M., Miyake K., Seya T. Establishment of a monoclonal antibody against human Toll-like receptor 3 that blocks double-stranded RNA-mediated signaling. Biochem. Biophys. Res. Commun. 2002;293:1364–1369. doi: 10.1016/S0006-291X(02)00380-7. PubMed DOI

Kim Y.M., Brinkmann M.M., Paquet M.E., Ploegh H.L. UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes. Nature. 2008;452:234–238. doi: 10.1038/nature06726. PubMed DOI

Pohar J., Pirher N., Benčina M., Manček-Keber M., Jerala R. The ectodomain of TLR3 receptor is required for its plasma membrane translocation. PLoS ONE. 2014;9:e92391. doi: 10.1371/journal.pone.0092391. PubMed DOI PMC

Schulz O., Diebold S.S., Chen M., Näslund T.I., Nolte M.A., Alexopoulou L., Azuma Y.T., Flavell R.A., Liljeström P., Reis e Souse C. Toll-like receptor 3 promotes cross-priming to virus-infected cells. Nature. 2005;433:887–892. doi: 10.1038/nature03326. PubMed DOI

Tabeta K., Georgel P., Janssen E., Du X., Hoebe K., Crozat K., Mudd S., Shamel L., Sovath S., Goode J., et al. Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proc. Natl. Acad. Sci. USA. 2004;101:3516–3521. doi: 10.1073/pnas.0400525101. PubMed DOI PMC

Reinert L.S., Harder L., Holm C.K., Iversen M.B., Horan K.A., Dagnæs-Hansen F., Ulhøi B.P., Holm T.H., Mogensen T.H., Owens T., et al. TLR3 deficiency renders astrocytes permissive to herpes simplex virus infection and facilitates establishment of CNS infection in mice. J. Clin. Investig. 2012;122:1368–1376. doi: 10.1172/JCI60893. PubMed DOI PMC

Lim H.K., Seppänen M., Hautala T., Ciancanelli M.J., Itan Y., Lafaille F.G., Dell W., Lorenzo L., Byun M., Pauwels E., et al. TLR3 deficiency in herpes simplex encephalitis: High allelic heterogeneity and recurrence risk. Neurology. 2014;83:1888–1897. doi: 10.1212/WNL.0000000000000999. PubMed DOI PMC

Abe Y., Fujii K., Nagata N., Takeuchi O., Akira S., Oshiumi H., Matsumoto M., Seya T., Koike S. The Toll-Like Receptor 3-Mediated Antiviral Response Is Important for Protection against Poliovirus Infection in Poliovirus Receptor Transgenic Mice. J. Virol. 2012;86:185–194. doi: 10.1128/JVI.05245-11. PubMed DOI PMC

Hardarson H.S., Baker J.S., Yang Z., Purevjav E., Huang C.H., Alexopoulou L., Li N., Flavell R.A., Bowles N.E., Vallejo J.G. Toll-like receptor 3 is an essential component of the innate stress response in virus-induced cardiac injury. Am. J. Physiol. Hear. Circ. Physiol. 2007;292:251–258. doi: 10.1152/ajpheart.00398.2006. PubMed DOI

Wang N., Liang Y., Devaraj S., Wang J., Lemon S.M., Li K. Toll-Like Receptor 3 Mediates Establishment of an Antiviral State against Hepatitis C Virus in Hepatoma Cells. J. Virol. 2009;83:9824–9834. doi: 10.1128/JVI.01125-09. PubMed DOI PMC

Von Herrath M. Diabetes: A virus-gene collaboration. Nature. 2009;459:518–519. doi: 10.1038/459518a. PubMed DOI

Shime H., Matsumoto M., Oshiumi H., Tanaka S., Nakane A., Iwakura Y., Tahara H., Inoue N., Seya T. Toll-like receptor 3 signaling converts tumor-supporting myeloid cells to tumoricidal effectors. Proc. Natl. Acad. Sci. USA. 2012;109:2066–2071. doi: 10.1073/pnas.1113099109. PubMed DOI PMC

Shime H., Matsumoto M., Seya T. Double-stranded RNA promotes CTL-independent tumor cytolysis mediated by CD11b+Ly6G+ intratumor myeloid cells through the TICAM-1 signaling pathway. Cell Death Differ. 2017;24:385–396. doi: 10.1038/cdd.2016.131. PubMed DOI PMC

Uhlen M., Bandrowski A., Carr S., Edwards A., Ellenberg J., Lundberg E., Rimm D.L., Rodriguez H., Hiltke T., Snyder M., et al. A proposal for validation of antibodies. Nat. Methods. 2016;13:823–827. doi: 10.1038/nmeth.3995. PubMed DOI PMC

Bonnin M., Fares N., Testoni B., Estornes Y., Weber K., Vanbervliet B., Lefrançois L., Gracia A., Kfoury A., Pez F., et al. Toll-like receptor 3 downregulation is an escape mechanism from apoptosis during hepatocarcinogenesis. J. Hepatol. 2019;71:763–772. doi: 10.1016/j.jhep.2019.05.031. PubMed DOI

González-Reyes S., Fernández J.M., González L.O., Aguirre A., Suárez A., González J.M., Escaff S., Vizoso F.J. Study of TLR3, TLR4, and TLR9 in prostate carcinomas and their association with biochemical recurrence. Cancer Immunol. Immunother. 2011;60:217–226. doi: 10.1007/s00262-010-0931-0. PubMed DOI PMC

González-Reyes S., Marín L., González L., González L.O., del Casar J.M., Lamelas M.L., González-Quintana J.M., Vizoso F.J. Study of TLR3, TLR4 and TLR9 in breast carcinomas and their association with metastasis. BMC Cancer. 2010;10:665. doi: 10.1186/1471-2407-10-665. PubMed DOI PMC

Salaun B., Zitvogel L., Asselin-Paturel C., Morel Y., Chemin K., Dubois C., Massacrier C., Conforti R., Chenard M.P., Sabourin J.C., et al. TLR3 as a biomarker for the therapeutic efficacy of double-stranded RNA in breast cancer. Cancer Res. 2011;71:1607–1614. doi: 10.1158/0008-5472.CAN-10-3490. PubMed DOI

Shi S., Xu C., Fang X., Zhang Y., Li H., Wen W., Yang G. Expression profile of Toll-like receptors in human breast cancer. Mol. Med. Rep. 2020;21:786–794. doi: 10.3892/mmr.2019.10853. PubMed DOI PMC

Salaun B., Lebecque S., Matikainen S., Rimoldi D., Romero P. Toll-like receptor 3 expressed by melanoma cells as a target for therapy? Clin. Cancer Res. 2007;13:4565–4574. doi: 10.1158/1078-0432.CCR-07-0274. PubMed DOI

Alkurdi L., Virard F., Vanbervliet B., Weber K., Toscano F., Bonnin M., Le Stang N., Lantuejoul S., Micheau O., Renno T., et al. Release of c-FLIP brake selectively sensitizes human cancer cells to TLR3-mediated apoptosis. Cell Death Dis. 2018;9:874. doi: 10.1038/s41419-018-0850-0. PubMed DOI PMC

Bianchi F., Alexiadis S., Camisaschi C., Truini M., Centonze G., Milione M., Balsari A., Tagliabue E., Sfondrini L. TLR3 expression induces apoptosis in human non-small-cell lung cancer. Int. J. Mol. Sci. 2020;21:1440. doi: 10.3390/ijms21041440. PubMed DOI PMC

Liu Y., Gu Y., Han Y., Zhang Q., Jiang Z., Zhang X., Huang B., Xu X., Zheng J., Cao X. Tumor Exosomal RNAs Promote Lung Pre-metastatic Niche Formation by Activating Alveolar Epithelial TLR3 to Recruit Neutrophils. Cancer Cell. 2016;30:243–256. doi: 10.1016/j.ccell.2016.06.021. PubMed DOI

Combaz-Lair C., Galateau-Sallé F., McLeer-Florin A., Le Stang N., David-Boudet L., Duruisseaux M., Ferretti G.R., Brambilla E., Lebecque S., Lantuejoul S. Immune biomarkers PD-1/PD-L1 and TLR3 in malignant pleural mesotheliomas. Hum. Pathol. 2016;52:9–18. doi: 10.1016/j.humpath.2016.01.010. PubMed DOI

Vanbervliet-Defrance B., Delaunay T., Daunizeau T., Kepenekian V., Glehen O., Weber K., Estornes Y., Ziverec A., Djemal L., Delphin M., et al. Cisplatin unleashes Toll-like receptor 3-mediated apoptosis through the downregulation of c-FLIP in malignant mesothelioma. Cancer Lett. 2020;472:29–39. doi: 10.1016/j.canlet.2019.12.016. PubMed DOI

Yuan M.M., Xu Y.Y., Chen L., Li X.Y., Qin J., Shen Y. TLR3 expression correlates with apoptosis, proliferation and angiogenesis in hepatocellular carcinoma and predicts prognosis. BMC Cancer. 2015;15:245. doi: 10.1186/s12885-015-1262-5. PubMed DOI PMC

Morikawa T., Sugiyama A., Kume H., Ota S., Kashima T., Tomita K., Kitamura T., Kodama T., Fukayama M., Aburatani H. Identification of Toll-Like Receptor 3 as a Potential Therapeutic Target in Clear Cell Renal Cell Carcinoma. Clin. Cancer Res. 2007;13:5703–5709. doi: 10.1158/1078-0432.CCR-07-0603. PubMed DOI

Zhou M., McFarland-Mancini M.M., Funk H.M., Husseinzadeh N., Mounajjed T., Drew A.F. Toll-like receptor expression in normal ovary and ovarian tumors. Cancer Immunol. Immunother. 2009;58:1375–1385. doi: 10.1007/s00262-008-0650-y. PubMed DOI PMC

Ding L., Ren J., Zhang D., Li Y., Huang X., Ji J., Hu Q., Wang H., Ni Y., Hou Y. The TLR3 agonist inhibit drug efflux and sequentially consolidates low-dose cisplatin-based chemoimmunotherapy while reducing side effects. Mol. Cancer Ther. 2017;16:1068–1079. doi: 10.1158/1535-7163.MCT-16-0454. PubMed DOI

Han S., Yin X., Wang Y., Xu W., Cheng W. Co-expression of HIF-1 and TLR3 is associated with poor prognosis in oral squamous cell carcinoma. Int. J. Clin. Exp. Pathol. 2020;13:65–72. PubMed PMC

Sheyhidin I., Nabi G., Hasim A., Zhang R.P., Ainiwaer J., Ma H., Wang H. Overexpression of TLR3, TLR4, TLR7 and TLR9 in esophageal squamous cell carcinoma. World J. Gastroenterol. 2011;17:3745–3751. doi: 10.3748/wjg.v17.i32.3745. PubMed DOI PMC

Helminen O., Huhta H., Lehenkari P.P., Saarnio J., Karttunen T.J., Kauppila J.H. Nucleic acid-sensing toll-like receptors 3, 7 and 8 in esophageal epithelium, barrett’s esophagus, dysplasia and adenocarcinoma. Oncoimmunology. 2016;5:e1127495. doi: 10.1080/2162402X.2015.1127495. PubMed DOI PMC

Fernandez-Garcia B., Eiró N., González-Reyes S., González L., Aguirre A., Gonzálea L.O., Del Casar J.M., García-Muñiz J.L., Vizoso F.J. Clinical significance of toll-like receptor 3, 4, and 9 in gastric cancer. J. Immunother. 2014;37:77–83. doi: 10.1097/CJI.0000000000000016. PubMed DOI

Salaun B., Coste I., Rissoan M.C., Lebecque S.J., Renno T. TLR3 Can Directly Trigger Apoptosis in Human Cancer Cells. J. Immunol. 2006;176:4894–4901. doi: 10.4049/jimmunol.176.8.4894. PubMed DOI

Harashima N., Inao T., Imamura R., Okano S., Suda T., Harada M. Roles of the PI3K/Akt pathway and autophagy in TLR3 signaling-induced apoptosis and growth arrest of human prostate cancer cells. Cancer Immunol. Immunother. 2012;61:667–676. doi: 10.1007/s00262-011-1132-1. PubMed DOI PMC

Gambara G., Desideri M., Stoppacciaro A., Padula F., De Cesaris P., Starace D., Tubaro A., Del Bufalo D., Filippini A., Ziparo E., et al. TLR3 engagement induces IRF-3-dependent apoptosis in androgen-sensitive prostate cancer cells and inhibits tumour growth in vivo. J. Cell Mol. Med. 2015;19:327–339. doi: 10.1111/jcmm.12379. PubMed DOI PMC

Estornes Y., Toscano F., Virard F., Jacquemin G., Pierrot A., Vanbervliet B., Bonnin M., Lalaoui N., Mercier-Gouy P., Pachéco Y., et al. dsRNA induces apoptosis through an atypical death complex associating TLR3 to caspase-8. Cell Death Differ. 2012;19:1482–1494. doi: 10.1038/cdd.2012.22. PubMed DOI PMC

Feoktistova M., Geserick P., Kellert B., Dimitrova D.P., Langlais C., Hupe M., Cain C., MacFarlane M., Häcker G., Leverkus M. cIAPs block Ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms. Mol. Cell. 2011;43:449–463. doi: 10.1016/j.molcel.2011.06.011. PubMed DOI PMC

Paone A., Starace D., Galli R., Padula F., De Cesaris P., Filippini A., Ziparo E., Riccioli A. Toll-like receptor 3 triggers apoptosis of human prostate cancer cells through a PKC-α-dependent mechanism. Carcinogenesis. 2008;29:1334–1342. doi: 10.1093/carcin/bgn149. PubMed DOI

Nomi N., Kodama S., Suzuki M. Toll-like receptor 3 signaling induces apoptosis in human head and neck cancer via survivin associated pathway. Oncol. Rep. 2010;24:225–231. doi: 10.3892/or_00000850. PubMed DOI

Weber A., Kirejczyk Z., Besch R., Potthoff S., Leverkus M., Häcker G. Proapoptotic signalling through toll-like receptor-3 involves TRIF-dependent activation of caspase-8 and is under the control of inhibitor of apoptosis proteins in melanoma cells. Cell Death Differ. 2010;17:942–951. doi: 10.1038/cdd.2009.190. PubMed DOI

Chuang H.C., Lin H.Y., Liao P.L., Huang C.C., Lin L.L., Hsu W.M., Chaung J.H. Immunomodulator polyinosinic-polycytidylic acid enhances the inhibitory effect of 13-cis-retinoic acid on neuroblastoma through a TLR3-related immunogenic-apoptotic response. Lab. Investig. 2020;100:606–618. doi: 10.1038/s41374-019-0356-0. PubMed DOI

Jia D., Yang W., Li L., Liu H., Tan Y., Ooi S., Chi L., Filion L.G., Figeys D., Wang L. β-Catenin and NF-κB co-activation triggered by TLR3 stimulation facilitates stem cell-like phenotypes in breast cancer. Cell Death Differ. 2015;22:298–310. doi: 10.1038/cdd.2014.145. PubMed DOI PMC

Bugge M., Bergstrom B., Eide O.K., Solli H., Kjønstad I.F., Stenvik J., Espevik T., Nilsen N.J. Surface toll-like receptor 3 expression in metastatic intestinal epithelial cells induces inflammatory cytokine production and promotes invasiveness. J. Biol. Chem. 2017;292:15408–15425. doi: 10.1074/jbc.M117.784090. PubMed DOI PMC

Paone A., Galli R., Gabellini C., Lukashev D., Starace D., Gorlach A., De Cesaris P., Ziparo E., Del Bufalo D., Sitkovsky M.V., et al. Toll-like Receptor 3 Regulates Angiogenesis and Apoptosis in Prostate Cancer Cell Lines through Hypoxia-Inducible Factor 1α. Neoplasia. 2010;12:539–549. doi: 10.1593/neo.92106. PubMed DOI PMC

Magnifico M.C., Macone A., Marani M., Bouzidi A., Giardina G., Rinaldo S., Cutruzzolà F., Paone A. Linking Infection and Prostate Cancer Progression: Toll-like Receptor3 Stimulation Rewires Glucose Metabolism in Prostate Cells. Anticancer Res. 2019;39:5541–5549. doi: 10.21873/anticanres.13747. PubMed DOI

Saxena M., Sabado R.L., Mar M.L., Mohri H., Salazar A.M., Dong H., Da Rosa J.C., Markowitz M., Bhardwaj N., Miller E. Poly-ICLC, a TLR3 agonist, induces transient innate immune responses in patients with treated HIV-infection: A randomized double-blinded placebo controlled trial. Front. Immunol. 2019;10:1–12. doi: 10.3389/fimmu.2019.00725. PubMed DOI PMC

Schlom J., Arlen P.M., Gulley J.L. Cancer vaccines: Moving beyond current paradigms. Clin. Cancer Res. 2007;13:3776–3782. doi: 10.1158/1078-0432.CCR-07-0588. PubMed DOI PMC

Zhao J., Xue Y., Pan Y., Yao A., Wang G., Li D., Wang T., Zhao S., Hou Y. Toll-like receptor 3 agonist poly I:C reinforces the potency of cytotoxic chemotherapy via the TLR3-UNC93B1-IFN-β signaling axis in paclitaxel-resistant colon cancer. J. Cell Physiol. 2019;234:7051–7061. doi: 10.1002/jcp.27459. PubMed DOI

Yoshida S., Shime H., Takeda Y., Nam J.M., Takashima K., Matsumoto M., Shirato H., Kasahara M., Seya T. Toll-like receptor 3 signal augments radiation-induced tumor growth retardation in a murine model. Cancer Sci. 2018;109:956–965. doi: 10.1111/cas.13543. PubMed DOI PMC

Wu Y., Huang W., Chen L., Jin M., Gao Z., An C., Lin H. Anti-tumor outcome evaluation against non-small cell lung cancer in vitro and in vivo using PolyI:C as nucleic acid therapeutic agent. Am. J. Transl. Res. 2019;11:1919–1937. PubMed PMC

Gierlich P., Lex V., Technau A., Keupp A., Morper L., Glunz A., Sennholz H., Rachor J., Sauer S., Marcu A., et al. Prostaglandin E2 in a TLR3- and 7/8-agonist-based DC maturation cocktail generates mature, cytokine-producing, migratory DCs but impairs antigen cross-presentation to CD8+ T cells. Cancer Immunol. Immunother. 2020;69:1029–1042. doi: 10.1007/s00262-019-02470-1. PubMed DOI PMC

Takeda Y., Kataoka K., Yamagishi J., Ogawa S., Seya T., Matsumoto M. A TLR3-Specific Adjuvant Relieves Innate Resistance to PD-L1 Blockade without Cytokine Toxicity in Tumor Vaccine Immunotherapy. Cell Rep. 2017;19:1874–1887. doi: 10.1016/j.celrep.2017.05.015. PubMed DOI

Schau I., Michen S., Hagstotz A., Janke A., Schackert G., Appelhans D., Temme A. Targeted delivery of TLR3 agonist to tumor cells with single chain antibody fragment-conjugated nanoparticles induces type I-interferon response and apoptosis. Sci. Rep. 2019;9:1–15. doi: 10.1038/s41598-019-40032-8. PubMed DOI PMC

Chuang H.C., Chou M.H., Chien C.Y., Chuang J.H., Liu Y.L. Triggering TLR3 pathway promotes tumor growth and cisplatin resistance in head and neck cancer cells. Oral Oncol. 2018;86:141–149. doi: 10.1016/j.oraloncology.2018.09.015. PubMed DOI

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...