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Targeting Toll-Like Receptors in Cancer Immunotherapy

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  • First Online:
Handbook of Cancer and Immunology

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Abstract

Recently, novel cancer immunotherapy approaches have gained rising interest. While chronic inflammation has been defined as a major hallmark of malignancy, acute and targeted inflammation may be able to stimulate the immune system to treat illnesses, such as cancer. Toll-like receptors (TLRs) are innate immune receptors that act as a bridge between innate and adaptive immune systems. These receptors can be expressed both within cellular compartments and on the cellular surface. For a long time, TLR binders have been used as adjuvants for conventional vaccines; Indeed, it appears that they can exert actions in promoting the efficacy of cancer immunotherapy. The application of approaches targeting TLRs to treat cancer now extends to more novel approaches of chimeric antigen receptor (CAR) T-cell and monoclonal antibodies. The aim of this chapter is to provide an overview on TLRs’ molecular pathways in immune cells, the influence of TLR stimulation in cancer immunotherapies, production of TLRs in various cancers, and ultimately, its role in mediation of tumor microenvironment and cancer progression.

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References

  • Abarca-Merlin DM, Maldonado-Bernal C, Alvarez-Arellano L (2019) Toll-like receptors as therapeutic targets in central nervous system tumors. Biomed Res Int 2019:5286358

    Article  CAS  Google Scholar 

  • Adams S (2009) Toll-like receptor agonists in cancer therapy. Immunotherapy 1:949–964

    Article  CAS  Google Scholar 

  • Adams M, Navabi H, Croston D, Coleman S, Tabi Z, Clayton A, Jasani B, Mason MD (2005) The rationale for combined chemo/immunotherapy using a Toll-like receptor 3 (TLR3) agonist and tumour-derived exosomes in advanced ovarian cancer. Vaccine 23:2374–2378

    Article  CAS  Google Scholar 

  • Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124:783–801

    Article  CAS  Google Scholar 

  • Anwar MA, Shah M, Kim J, Choi S (2019) Recent clinical trends in Toll-like receptor targeting therapeutics. Med Res Rev 39:1053–1090

    Article  CAS  Google Scholar 

  • Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, Mignot G, Maiuri MC, Ullrich E, Saulnier P (2007) Toll-like receptor 4–dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med 13:1050–1059

    Article  CAS  Google Scholar 

  • Banday AH, Jeelani S, Hruby VJ (2015) Cancer vaccine adjuvants–recent clinical progress and future perspectives. Immunopharmacol Immunotoxicol 37:1–11

    Article  CAS  Google Scholar 

  • Baselga J, Perez EA, Pienkowski T, Bell R (2006) Adjuvant trastuzumab: a milestone in the treatment of HER-2-positive early breast cancer. Oncologist 11:4–12

    Article  CAS  Google Scholar 

  • Berk E, Xu S, Czerniecki BJ (2014) Dendritic cells matured in the presence of TLR ligands overcome the immunosuppressive functions of regulatory T cells. Oncoimmunology 3:e27617

    Article  Google Scholar 

  • Blasius AL, Beutler B (2010) Intracellular toll-like receptors. Immunity 32:305–315

    Article  CAS  Google Scholar 

  • Boozari M, Butler AE, Sahebkar A (2019) Impact of curcumin on toll-like receptors. J Cell Physiol 234:12471–12482

    Article  CAS  Google Scholar 

  • Bourquin C, Schmidt L, Lanz A-L, Storch B, Wurzenberger C, Anz D, Sandholzer N, Mocikat R, Berger M, Poeck H (2009) Immunostimulatory RNA oligonucleotides induce an effective antitumoral NK cell response through the TLR7. J Immunol 183:6078–6086

    Article  CAS  Google Scholar 

  • Bourquin C, Pommier A, Hotz C (2020) Harnessing the immune system to fight cancer with Toll-like receptor and RIG-I-like receptor agonists. Pharmacol Res 154:104192

    Article  CAS  Google Scholar 

  • Carbone C, Piro G, Agostini A, Delfino P, De Sanctis F, Nasca V, Spallotta F, Sette C, Martini M, Ugel S, Corbo V, Cappello P, Bria E, Scarpa A, Tortora G (2021) Intratumoral injection of TLR9 agonist promotes an immunopermissive microenvironment transition and causes cooperative antitumor activity in combination with anti-PD1 in pancreatic cancer. J Immunother Cancer 9

    Google Scholar 

  • Cheadle EJ, Lipowska-Bhalla G, Dovedi SJ, Fagnano E, Klein C, Honeychurch J, Illidge TM (2017) A TLR7 agonist enhances the antitumor efficacy of obinutuzumab in murine lymphoma models via NK cells and CD4 T cells. Leukemia 31:1611–1621

    Article  CAS  Google Scholar 

  • Cherfils-Vicini J, Iltis C, Cervera L, Pisano S, Croce O, Sadouni N, Győrffy B, Collet R, Renault VM, Rey-Millet M (2019) Cancer cells induce immune escape via glycocalyx changes controlled by the telomeric protein TRF 2. EMBO J 38:e100012

    Article  Google Scholar 

  • Chuang Y-C, Tseng J-C, Huang L-R, Huang C-M, Huang C-YF, Chuang T-H (2020) Adjuvant effect of toll-like receptor 9 activation on cancer immunotherapy using checkpoint blockade. Front Immunol 11:1075

    Article  CAS  Google Scholar 

  • Cluff CW (2009) Monophosphoryl lipid A (MPL) as an adjuvant for anti-cancer vaccines: clinical results. Lipid A in cancer therapy. Springer, pp 111–123

    Google Scholar 

  • Coiffier B, Lepage E, Brière J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P (2002) CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346:235–242

    Article  CAS  Google Scholar 

  • Coleman MM, Keane J, Mills KH (2010) Tregs and BCG—dangerous liaisons in TB. Citeseer 88:1067–1069

    CAS  Google Scholar 

  • Cui L, Wang X, Zhang D (2021) TLRs as a promise target along with immune checkpoint against gastric cancer. Front Cell Dev Biol 8:611444–611444

    Article  Google Scholar 

  • Curtin JF, King GD, Barcia C, Liu C, Hubert FX, Guillonneau C, Josien R, Anegon I, Lowenstein PR, Castro MG (2006) Fms-like tyrosine kinase 3 ligand recruits plasmacytoid dendritic cells to the brain. J Immunol 176:3566–3577

    Article  CAS  Google Scholar 

  • Curtin J, Liu N, Candolfi M, Xiong W, Assi H, Yagiz K, Edwards M, Michelsen K, Kroeger K, Liu C (2009) HMGB1 mediates endogenous TLR2 activation and brain tumor regression. PLoS Med 6:e10

    Article  Google Scholar 

  • Deng Y, Yang J, Qian J, Liu R, Huang E, Wang Y, Luo F, Chu Y (2019) TLR1/TLR2 signaling blocks the suppression of monocytic myeloid-derived suppressor cell by promoting its differentiation into M1-type macrophage. Mol Immunol 112:266–273

    Article  CAS  Google Scholar 

  • Diefenbach A, Raulet DH (2002) The innate immune response to tumors and its role in the induction of T-cell immunity. Immunol Rev 188:9–21

    Article  CAS  Google Scholar 

  • Dietsch GN, Lu H, Yang Y, Morishima C, Chow LQ, Disis ML, Hershberg RM (2016) Coordinated activation of toll-like receptor8 (TLR8) and NLRP3 by the TLR8 agonist, VTX-2337, ignites tumoricidal natural killer cell activity. PLoS One 11:e0148764

    Article  Google Scholar 

  • Farkona S, Diamandis EP, Blasutig IM (2016) Cancer immunotherapy: the beginning of the end of cancer? BMC Med 14:1–18

    Article  Google Scholar 

  • Friedberg JW, Kim H, McCauley M, Hessel EM, Sims P, Fisher DC, Nadler LM, Coffman RL, Freedman AS (2005) Combination immunotherapy with a CpG oligonucleotide (1018 ISS) and rituximab in patients with non-Hodgkin lymphoma: increased interferon-α/β–inducible gene expression, without significant toxicity. Blood 105:489–495

    Article  CAS  Google Scholar 

  • Gilliet M, Cao W, Liu Y-J (2008) Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases. Nat Rev Immunol 8:594–606

    Article  CAS  Google Scholar 

  • Grauer OM, Molling JW, Bennink E, Toonen LW, Sutmuller RP, Nierkens S, Adema GJ (2008) TLR ligands in the local treatment of established intracerebral murine gliomas. J Immunol 181:6720–6729

    Article  CAS  Google Scholar 

  • Guha M (2012) Anticancer TLR agonists on the ropes: toll-like receptor agonists have hit another setback with the Phase II failure of Idera’s IMO-2055, but these immunotherapies may still make a comeback if appropriate combinations with vaccine antigens or anticancer drugs can be identified. Nat Rev Drug Discov 11:503–506

    Article  Google Scholar 

  • Guillerey C, Chow MT, Miles K, Olver S, Sceneay J, Takeda K, Möller A, Smyth MJ (2015) Toll-like receptor 3 regulates NK cell responses to cytokines and controls experimental metastasis. Oncoimmunology 4:e1027468

    Article  Google Scholar 

  • Hallek M, Fischer K, Fingerle-Rowson G, Fink A, Busch R, Mayer J, Hensel M, Hopfinger G, Hess G, Von Grünhagen U (2010) Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 376:1164–1174

    Article  CAS  Google Scholar 

  • Han HD, Byeon Y, Kang TH, Jung ID, Lee J-W, Shin BC, Lee YJ, Sood AK, Park Y-M (2016) Toll-like receptor 3-induced immune response by poly (d, l-lactide-co-glycolide) nanoparticles for dendritic cell-based cancer immunotherapy. Int J Nanomedicine 11:5729

    Article  CAS  Google Scholar 

  • Han D, Xu Z, Zhuang Y, Ye Z, Qian Q (2021) Current progress in CAR-T cell therapy for hematological malignancies. J Cancer 12:326

    Article  CAS  Google Scholar 

  • Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K, Horiuchi T, Tomizawa H, Takeda K, Akira S (2002) Small anti-viral compounds activate immune cells via the TLR7 MyD88–dependent signaling pathway. Nat Immunol 3:196–200

    Article  CAS  Google Scholar 

  • Huang B, Zhao J, Unkeless J, Feng Z, Xiong H (2008) TLR signaling by tumor and immune cells: a double-edged sword. Oncogene 27:218–224

    Article  CAS  Google Scholar 

  • Huang L, Xu H, Peng G (2018) TLR-mediated metabolic reprogramming in the tumor microenvironment: potential novel strategies for cancer immunotherapy. Cell Mol Immunol 15:428–437

    Article  CAS  Google Scholar 

  • Hudis CA (2007) Trastuzumab—mechanism of action and use in clinical practice. N Engl J Med 357:39–51

    Article  CAS  Google Scholar 

  • Iqbal NT, Hussain R (2014) Non-specific immunity of BCG vaccine: a perspective of BCG immunotherapy. Trials Vaccinol 3:143–149

    Article  Google Scholar 

  • Iribarren K, Bloy N, Buqué A, Cremer I, Eggermont A, Fridman WH, Fucikova J, Galon J, Špíšek R, Zitvogel L (2016) Trial Watch: immunostimulation with Toll-like receptor agonists in cancer therapy. Oncoimmunology 5:e1088631

    Article  Google Scholar 

  • Ito H, Ando T, Arioka Y, Saito K, Seishima M (2015) Inhibition of indoleamine 2, 3-dioxygenase activity enhances the anti-tumour effects of a Toll-like receptor 7 agonist in an established cancer model. Immunology 144:621–630

    Article  CAS  Google Scholar 

  • Jasani B, Navabi H, Adams M (2009) Ampligen: a potential toll-like 3 receptor adjuvant for immunotherapy of cancer. Vaccine 27:3401–3404

    Article  CAS  Google Scholar 

  • Kaifu T, Escalière B, Gastinel LN, Vivier E, Baratin M (2011) B7-H6/NKp30 interaction: a mechanism of alerting NK cells against tumors. Cell Mol Life Sci 68:3531–3539

    Article  CAS  Google Scholar 

  • Karki K, Pande D, Negi R, Khanna S, Khanna RS, Khanna HD (2015) Correlation of serum toll like receptor 9 and trace elements with lipid peroxidation in the patients of breast diseases. J Trace Elem Med Biol 30:11–16

    Article  CAS  Google Scholar 

  • Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11:373–384

    Article  CAS  Google Scholar 

  • Kim S-Y, Kim S, Kim J-E, Lee SN, Shin IW, Shin HS, Jin SM, Noh Y-W, Kang YJ, Kim YS (2019) Lyophilizable and multifaceted toll-like receptor 7/8 agonist-loaded nanoemulsion for the reprogramming of tumor microenvironments and enhanced cancer immunotherapy. ACS Nano 13:12671–12686

    Article  CAS  Google Scholar 

  • Krieg AM (2007) Development of TLR9 agonists for cancer therapy. J Clin Invest 117:1184–1194

    Article  CAS  Google Scholar 

  • Lambert SL, Yang C-F, Liu Z, Sweetwood R, Zhao J, Cheng L, Jin H, Woo J (2012) Molecular and cellular response profiles induced by the TLR4 agonist-based adjuvant Glucopyranosyl Lipid A. PLoS One 7:e51618

    Article  CAS  Google Scholar 

  • LaRue H, Ayari C, Bergeron A, Fradet Y (2013) Toll-like receptors in urothelial cells—targets for cancer immunotherapy. Nat Rev Urol 10:537–545

    Article  CAS  Google Scholar 

  • Lee MK IV, Xu S, Fitzpatrick EH, Sharma A, Graves HL, Czerniecki BJ (2013) Inhibition of CD4+ CD25+ regulatory T cell function and conversion into Th1-like effectors by a Toll-like receptor-activated dendritic cell vaccine. PLoS One 8:e74698

    Article  CAS  Google Scholar 

  • Lee SN, Jin SM, Shin HS, Lim YT (2020) Chemical strategies to enhance the therapeutic efficacy of toll-like receptor agonist based cancer immunotherapy. Acc Chem Res 53:2081–2093

    Article  CAS  Google Scholar 

  • Li JK, Balic JJ, Yu L, Jenkins B (2017) TLR agonists as adjuvants for cancer vaccines. Adv Exp Med Biol 1024:195–212

    Article  CAS  Google Scholar 

  • Liang Z, Cui X, Yang L, Hu Q, Li D, Zhang X, Han L, Shi S, Shen Y, Zhao W, Ju Q, Deng X, Wu Y, Sheng W (2021) Co-assembled nanocomplexes of peptide neoantigen Adpgk and Toll-like receptor 9 agonist CpG ODN for efficient colorectal cancer immunotherapy. Int J Pharm 608:121091

    Article  CAS  Google Scholar 

  • Liao G, Lv J, Ji A, Meng S, Chen C (2021) TLR3 serves as a prognostic biomarker and associates with immune infiltration in the renal clear cell carcinoma microenvironment. J Oncol 2021:3336770

    Article  Google Scholar 

  • Lim K-H, Staudt LM (2013) Toll-like receptor signaling. Cold Spring Harb Perspect Biol 5:a011247

    Article  Google Scholar 

  • Lin S-C, Lo Y-C, Wu H (2010) Helical assembly in the MyD88–IRAK4–IRAK2 complex in TLR/IL-1R signalling. Nature 465:885–890

    Article  CAS  Google Scholar 

  • Lu H, Yang Y, Gad E, Inatsuka C, Wenner CA, Disis ML, Standish LJ (2011) TLR2 agonist PSK activates human NK cells and enhances the antitumor effect of HER2-targeted monoclonal antibody therapy. Clin Cancer Res 17:6742–6753

    Article  CAS  Google Scholar 

  • Lu H, Dietsch GN, Matthews M-AH, Yang Y, Ghanekar S, Inokuma M, Suni M, Maino VC, Henderson KE, Howbert JJ (2012) VTX-2337 is a novel TLR8 agonist that activates NK cells and augments ADCC. Clin Cancer Res 18:499–509

    Article  CAS  Google Scholar 

  • Lu H, Hewitt J, ter Meulen J (2016) Intratumoral injection of G100 (TLR4 agonist glycopyranosyl lipid A) modulates tumor microenvironment and induces CD8 T cell-dependent, systemic anti-tumor immunity. AACR

    Google Scholar 

  • Manches O, Munn D, Fallahi A, Lifson J, Chaperot L, Plumas J, Bhardwaj N (2008) HIV-activated human plasmacytoid DCs induce Tregs through an indoleamine 2, 3-dioxygenase–dependent mechanism. J Clin Invest 118:3431–3439

    Article  CAS  Google Scholar 

  • Manna E (2016) Toll-like receptor: breast cancer development and immunotherapy. Arch Can Res 4:3

    Article  Google Scholar 

  • Manome Y, Suzuki D, Nishida R, Yamada A, Miyamoto Y, Funatsu T, Kamijo R (2019) Immunotherapy for malignant tumors with focus on toll-like receptors. Oral Sci Int 16:3–7

    Article  Google Scholar 

  • Matsumoto M, Takeda Y, Seya T (2020) Targeting Toll-like receptor 3 in dendritic cells for cancer immunotherapy. Expert Opin Biol Ther 20:937–946

    Article  CAS  Google Scholar 

  • Matzner P, Sorski L, Shaashua L, Elbaz E, Lavon H, Melamed R, Rosenne E, Gotlieb N, Benbenishty A, Reed SG (2016) Perioperative treatment with the new synthetic TLR-4 agonist GLA-SE reduces cancer metastasis without adverse effects. Int J Cancer 138:1754–1764

    Article  CAS  Google Scholar 

  • Mett V, Komarova E, Greene K, Bespalov I, Brackett C, Gillard B, Gleiberman A, Toshkov I, Aygün-Sunar S, Johnson C (2018) Mobilan: a recombinant adenovirus carrying Toll-like receptor 5 self-activating cassette for cancer immunotherapy. Oncogene 37:439–449

    Article  CAS  Google Scholar 

  • Mohseni Afshar Z, Babazadeh A, Janbakhsh A, Afsharian M, Saleki K, Barary M, Ebrahimpour S (2021) Vaccine-induced immune thrombotic thrombocytopenia after vaccination against Covid-19: a clinical dilemma for clinicians and patients. Rev Med Virol:e2273

    Google Scholar 

  • Mount A, Koernig S, Silva A, Drane D, Maraskovsky E, Morelli AB (2013) Combination of adjuvants: the future of vaccine design. Expert Rev Vaccines 12:733–746

    Article  CAS  Google Scholar 

  • Muccioli M, Benencia F (2014) Toll-like receptors in ovarian cancer as targets for immunotherapies. Front Immunol 5:341

    Article  Google Scholar 

  • Nicodemus CF, Wang L, Lucas J, Varghese B, Berek JS (2010) Toll-like receptor-3 as a target to enhance bioactivity of cancer immunotherapy. Am J Obstet Gynecol 202:608. e601-608. e608

    Article  Google Scholar 

  • Noh J-Y, Yoon SR, Kim T-D, Choi I, Jung H (2020) Toll-like receptors in natural killer cells and their application for immunotherapy. J Immunol Res 2020:2045860

    Article  Google Scholar 

  • Ohadian Moghadam S, Nowroozi MR (2019) Toll-like receptors: the role in bladder cancer development, progression and immunotherapy. Scand J Immunol 90:e12818

    Article  Google Scholar 

  • Ovchinnikova O, Berge N, Kang C, Urien C, Ketelhuth D, Pottier J, Drouet L, Hansson G, Marchal G, Bäck M (2014) Mycobacterium bovis BCG killed by extended freeze-drying induces an immunoregulatory profile and protects against atherosclerosis. J Intern Med 275:49–58

    Article  CAS  Google Scholar 

  • Pahlavanneshan S, Sayadmanesh A, Ebrahimiyan H, Basiri M (2021) Toll-like receptor-based strategies for cancer immunotherapy. J Immunol Res 2021:9912188

    Article  Google Scholar 

  • Rahmani A, Baee M, Saleki K, Moradi S, Nouri HR (2021) Applying high throughput and comprehensive immunoinformatics approaches to design a trivalent subunit vaccine for induction of immune response against emerging human coronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2. J Biomol Struct Dyn:1–17

    Google Scholar 

  • Ribas A, Wolchok JD (2018) Cancer immunotherapy using checkpoint blockade. Science 359:1350–1355

    Article  CAS  Google Scholar 

  • Ridnour LA, Cheng RY, Switzer CH, Heinecke JL, Ambs S, Glynn S, Young HA, Trinchieri G, Wink DA (2013) Molecular pathways: toll-like receptors in the tumor microenvironment—poor prognosis or new therapeutic opportunity. Clin Cancer Res 19:1340–1346

    Article  CAS  Google Scholar 

  • Saleki K, Yaribash S, Banazadeh M, Hajihosseinlou E, Gouravani M, Saghazadeh A, Rezaei N (2021) Interferon therapy in patients with SARS, MERS, and COVID-19: a systematic review and meta-analysis of clinical studies. Eur J Pharmacol 906:174248

    Article  CAS  Google Scholar 

  • Schreibelt G, Tel J, Sliepen KH, Benitez-Ribas D, Figdor CG, Adema GJ, de Vries IJM (2010) Toll-like receptor expression and function in human dendritic cell subsets: implications for dendritic cell-based anti-cancer immunotherapy. Cancer Immunol Immunother 59:1573–1582

    Article  CAS  Google Scholar 

  • Seya T, Shime H, Takeda Y, Tatematsu M, Takashima K, Matsumoto M (2015) Adjuvant for vaccine immunotherapy of cancer–focusing on Toll-like receptor 2 and 3 agonists for safely enhancing antitumor immunity. Cancer Sci 106:1659–1668

    Article  CAS  Google Scholar 

  • Shi M, Chen X, Ye K, Yao Y, Li Y (2016) Application potential of toll-like receptors in cancer immunotherapy: systematic review. Medicine 95

    Google Scholar 

  • Shime H, Maruyama A, Yoshida S, Takeda Y, Matsumoto M, Seya T (2018) Toll-like receptor 2 ligand and interferon-γ suppress anti-tumor T cell responses by enhancing the immunosuppressive activity of monocytic myeloid-derived suppressor cells. Oncoimmunology 7:e1373231

    Article  Google Scholar 

  • Sitkovsky M, Lukashev D (2005) Regulation of immune cells by local-tissue oxygen tension: HIF1α and adenosine receptors. Nat Rev Immunol 5:712–721

    Article  CAS  Google Scholar 

  • Sitkovsky MV, Kjaergaard J, Lukashev D, Ohta A (2008) Hypoxia-adenosinergic immunosuppression: tumor protection by T regulatory cells and cancerous tissue hypoxia. Clin Cancer Res 14:5947–5952

    Article  CAS  Google Scholar 

  • Smith M, García-Martínez E, Pitter MR, Fucikova J, Spisek R, Zitvogel L, Kroemer G, Galluzzi L (2018) Trial watch: toll-like receptor agonists in cancer immunotherapy. Oncoimmunology 7:e1526250

    Article  Google Scholar 

  • Smits EL, Ponsaerts P, Berneman ZN, Van Tendeloo VF (2008) The use of TLR7 and TLR8 ligands for the enhancement of cancer immunotherapy. Oncologist 13:859–875

    Article  CAS  Google Scholar 

  • Su X, Ye J, Hsueh EC, Zhang Y, Hoft DF, Peng G (2010) Tumor microenvironments direct the recruitment and expansion of human Th17 cells. J Immunol 184:1630–1641

    Article  CAS  Google Scholar 

  • Takeshita F, Leifer CA, Gursel I, Ishii KJ, Takeshita S, Gursel M, Klinman DM (2001) Cutting edge: role of Toll-like receptor 9 in CpG DNA-induced activation of human cells. J Immunol 167:3555–3558

    Article  CAS  Google Scholar 

  • Tanaka A, Sakaguchi S (2017) Regulatory T cells in cancer immunotherapy. Cell Res 27:109–118

    Article  CAS  Google Scholar 

  • Tcyganov E, Mastio J, Chen E, Gabrilovich DI (2018) Plasticity of myeloid-derived suppressor cells in cancer. Curr Opin Immunol 51:76–82

    Article  CAS  Google Scholar 

  • Tran TH, Tran TTP, Truong DH, Nguyen HT, Pham TT, Yong CS, Kim JO (2019) Toll-like receptor-targeted particles: a paradigm to manipulate the tumor microenvironment for cancer immunotherapy. Acta Biomater 94:82–96

    Article  CAS  Google Scholar 

  • Tsukamoto H, Kubota K, Shichiku A, Maekawa M, Mano N, Yagita H, Ohta S, Tomioka Y (2019) An agonistic anti-Toll-like receptor 4 monoclonal antibody as an effective adjuvant for cancer immunotherapy. Immunology 158:136–149

    Article  CAS  Google Scholar 

  • Urban-Wojciuk Z, Khan MM, Oyler BL, Fåhraeus R, Marek-Trzonkowska N, Nita-Lazar A, Hupp TR, Goodlett DR (2019) The role of TLRs in anti-cancer immunity and tumor rejection. Front Immunol 10

    Google Scholar 

  • Vacchelli E, Galluzzi L, Eggermont A, Fridman WH, Galon J, Sautès-Fridman C, Tartour E, Zitvogel L, Kroemer G (2012) Trial watch: FDA-approved Toll-like receptor agonists for cancer therapy. Oncoimmunology 1:894–907

    Article  Google Scholar 

  • Veyrat M, Durand S, Classe M, Glavan TM, Oker N, Kapetanakis N-I, Jiang X, Gelin A, Herman P, Casiraghi O (2016) Stimulation of the toll-like receptor 3 promotes metabolic reprogramming in head and neck carcinoma cells. Oncotarget 7:82580

    Article  Google Scholar 

  • Von Bubnoff D, Scheler M, Wilms H, Fimmers R, Bieber T (2011) Identification of IDO-positive and IDO-negative human dendritic cells after activation by various proinflammatory stimuli. J Immunol 186:6701–6709

    Article  Google Scholar 

  • Wang C, Deng L, Hong M, Akkaraju GR, Inoue J-i, Chen ZJ (2001) TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412:346–351

    Article  CAS  Google Scholar 

  • Whiteside T (2008) The tumor microenvironment and its role in promoting tumor growth. Oncogene 27:5904–5912

    Article  CAS  Google Scholar 

  • Wicherska-Pawłowska K, Wróbel T, Rybka J (2021) Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs) in innate immunity. TLRs, NLRs, and RLRs ligands as immunotherapeutic agents for hematopoietic diseases. Int J Mol Sci 22

    Google Scholar 

  • Wiedemann GM, Jacobi SJ, Chaloupka M, Krächan A, Hamm S, Strobl S, Baumgartner R, Rothenfusser S, Duewell P, Endres S (2016) A novel TLR7 agonist reverses NK cell anergy and cures RMA-S lymphoma-bearing mice. Oncoimmunology 5:e1189051

    Article  Google Scholar 

  • Ye J, Peng G (2015) Controlling T cell senescence in the tumor microenvironment for tumor immunotherapy. Oncoimmunology 4:e994398

    Article  Google Scholar 

  • Ye J, Ma C, Hsueh EC, Dou J, Mo W, Liu S, Han B, Huang Y, Zhang Y, Varvares MA (2014) TLR 8 signaling enhances tumor immunity by preventing tumor-induced T-cell senescence. EMBO Mol Med 6:1294–1311

    Article  CAS  Google Scholar 

  • Yentz S, Smith D (2018) Indoleamine 2, 3-dioxygenase (IDO) inhibition as a strategy to augment cancer immunotherapy. BioDrugs 32:311–317

    Article  CAS  Google Scholar 

  • Yusuf N (2014) Toll-like receptor mediated regulation of breast cancer: a case of mixed blessings. Front Immunol 5:224–224

    Google Scholar 

  • Zaini RG, Al-Rehaili AA (2019) The therapeutic strategies of regulatory T cells in malignancies and stem cell transplantations. J Oncol 2019

    Google Scholar 

  • Zhou H, Jiang M, Yuan H, Ni W, Tai G (2021) Dual roles of myeloid-derived suppressor cells induced by Toll-like receptor signaling in cancer. Oncol Lett 21:1–1

    Article  CAS  Google Scholar 

  • Zou W (2006) Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 6:295–307

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Student Research Committee, Babol University of Medical Sciences, Babol, Iran

    Kiarash Saleki

  2. USERN Office, Babol University of Medical Sciences, Babol, Iran

    Kiarash Saleki

  3. Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran

    Nima Rezaei

  4. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Nima Rezaei

  5. Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Stockholm, Sweden

    Nima Rezaei

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Correspondence to Nima Rezaei .

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  1. Division of Clinical Immunology, Karolinska University Hospital, Huddinge, Sweden

    Nima Rezaei

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Saleki, K., Rezaei, N. (2023). Targeting Toll-Like Receptors in Cancer Immunotherapy. In: Rezaei, N. (eds) Handbook of Cancer and Immunology. Springer, Cham. https://doi.org/10.1007/978-3-030-80962-1_192-1

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  • DOI: https://doi.org/10.1007/978-3-030-80962-1_192-1

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  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-80962-1

  • Online ISBN: 978-3-030-80962-1

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

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