Skip to main content

Advertisement

SpringerLink
Log in

Lung cancer and Toll-like receptors

  • Review
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Lung carcinoma is one of the leading causes of death worldwide. It is a non-immunogenic cancer, resistant to immune surveillance. Toll-like receptors (TLRs) connect the innate to the adaptive immune system. Given that cancerous cells evade the immune system, the activation of TLRs could represent a potential target for cancer therapy. The induction of Th1-like and cytotoxic immunity by TLR signalling could lead to tumour cell death, resulting in tumour regression or arrest. However, basic research and clinical trials revealed that the activation of specific TLRs, such as TLR2, TLR4 and TLR9, do not have any anti-tumour activity in lung carcinoma. Increasing evidence suggests that TLRs are important regulators of tumour biology; however, little is known about their function in lung cancer. Thus, in order to develop new therapeutic approaches, further studies are needed to understand the connection between TLRs and lung cancer progression. This review focuses on the potential mechanisms by which TLR ligands can facilitate or not lung cancer and lung metastases establishment/progression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

TLRs:

Toll-like receptors

MyD88:

Myeloid differentiation factor

TRIF:

TIR-domain-containing adapter-inducing interferon-β

PAMPs:

Pathogen-associated molecular patterns

DAMPs:

Danger-associated molecular patterns

DCs:

Dendritic cells

(pDCs):

Plasmacytoid dendritic cells

hsp:

Heat shock proteins

Treg:

T regulatory cells

IDO:

Indoleamine-2, 3-dyoxigenase

HMGB1:

High-mobility group box 1

References

  1. Jahrsdorfer B, Weiner GJ (2008) CpG oligodeoxynucleotides as immunotherapy in cancer. Cancer Ther 3(1):27–32

    Google Scholar 

  2. Igney FH, Krammer PH (2002) Immune escape of tumors: apoptosis resistance and tumor counterattack. J Leuk Biol 71(6):07–20

    Google Scholar 

  3. Prendergast GC (2008) Immune escape as a fundamental trait of cancer: focus on IDO. Oncogene 27(28):3889–3900

    Article  PubMed  CAS  Google Scholar 

  4. Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A (2009) Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 30(7):1073–1081

    Article  PubMed  CAS  Google Scholar 

  5. Wang RF, Peng G, Wang HY (2006) Regulatory T cells and toll-like receptors in tumor immunity. Semin Immunol 18:136–142

    Article  PubMed  CAS  Google Scholar 

  6. Mitchell JA, Paul-Clark MJ, Clarke GW, McMaster SK, Cartwright N (2007) Critical role of toll-like receptors and nucleotide oligomerisation domain in the regulation of health and disease. J Endocrinol 193(3):323–330

    Article  PubMed  CAS  Google Scholar 

  7. Kluwe J, Mencin A, Schwabe RF (2009) Toll like receptors, Wound healing and carcinogenesis. J mol Med 87(2):125–138

    Article  PubMed  CAS  Google Scholar 

  8. Rakoff-Nahoum S, Medzhitov R (2009) Toll-like receptors and cancer. Nat Rev Cancer 9(1):57–63

    Article  PubMed  CAS  Google Scholar 

  9. Sorrentino R, de Souza PM, Sriskandan S, Duffin C, Paul-Clark MJ, Mitchell JA (2008) Pattern recognition receptors and interleukin-8 mediate effects of Gram-positive and Gram-negative bacteria on lung epithelial cell function. Br J Pharmacol 154(4):864–871

    Article  PubMed  CAS  Google Scholar 

  10. Iwamura C, Nakayama T (2008) Toll-like receptors in the respiratory system: their roles in inflammation. Curr Allergy Asthma Rep 8(1):7–13

    Article  PubMed  CAS  Google Scholar 

  11. Yu L, Chen S (2008) Toll-like receptors expressed in tumour cells: targets for therapy. Cancer Immunol Immunther 57:1271–1278

    Article  CAS  Google Scholar 

  12. Cherfils-Vicini J, Platonova S, Gillard M, Laurans L, Validire P, Caliandro R, Magdeleinat P, Mami-Chouaib F, Dieu-Nosjean MC, Fridman WH, Damotte D, Sautès-Fridman C, Cremer I (2010) Triggering of TLR7 and TLR8 expressed by human lung cancer cells induces cell survival and chemoresistance. J Clin Invest 120(4):1285–1297

    Article  PubMed  CAS  Google Scholar 

  13. Koff JL, Shao MX, Ueki IF, Nadel JA (2008) Multiple TLRs activate EGFR via a signalling cascade to produce innate immune responses in airway epithelium. Am J Physiol Lung Cell Mol Physiol 294:L1068–L1075

    Article  PubMed  CAS  Google Scholar 

  14. Lechmann M, Zinser E, Golka A, Steinkasserer A (2002) Role of CD83 in the immunomodulation of dendritic cells. Int Arch Allergy Immunol 129(2):113–118

    Article  PubMed  CAS  Google Scholar 

  15. Doganci A, Eigenbrod T, Krug N, De Sanctis GT, Hausding M, Erpenbeck VJ, Haddad El-B, Lehr HA, Schmitt E, Bopp T, Kallen KJ, Herz U, Schmitt S, Luft C, Hecht O, Hohlfeld JM, Ito H, Nishimoto N, Yoshizaki K, Kishimoto T, Rose-John S, Renz H, Neurath MF, Galle PR, Finotto S (2005) The IL-6R alpha chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in vivo. J Clin Invest 115(2):313–325

    PubMed  CAS  Google Scholar 

  16. Reiner S, Sallusto F, Lanzavecchia A (2007) Division of labor with a workforce of one: challenges in specifying effector and memory T cell fate. Science 317:622–625

    Article  PubMed  CAS  Google Scholar 

  17. Wang L, Yi T, Kortylewski M, Pardoll DM, Zeng D, Yu H (2009) IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J Exp Med 206(7):1457–1464

    Article  PubMed  CAS  Google Scholar 

  18. Martin-Orozco N, Muranski P, Chung Y, Yang XO, Yamazaki T, Lu S, Hwu P, Restifo NP, Overwijk WW, Dong C (2009) T helper 17 cells promote cytotoxic T cell activation in tumor immunity. Immunity 31(5):787–798

    Article  PubMed  CAS  Google Scholar 

  19. Shepard HM, Brdlik CM, Schreiber H (2008) Signal integration: a framework for understanding the efficacy of therapeutics targeting the human EGFR family. J Clin Invest 118(11):3574–3581

    Article  PubMed  CAS  Google Scholar 

  20. Eisenbarth SC, Piggott DA, Bottomly K (2003) The master regulators of allergic inflammation: dendritic cells in Th2 sensitization. Curr Opin Immunol 15(6):620–626

    Article  PubMed  CAS  Google Scholar 

  21. Piggott DA, Eisenbarth SC, Xu L, Constant SL, Huleatt JW, Herrick CA, Bottomly K (2005) MyD88-dependent induction of allergic Th2 responses to intranasal antigen. J Clin Invest 115(2):459–467

    PubMed  CAS  Google Scholar 

  22. Sorrentino R, Morello S, Luciano A, Crother TR, Maiolino P, Bonavita E, Arra C, Adcock IM, Arditi M, Pinto A (2010) Plasmacytoid dendritic cells alter the antitumor activity of CpG-oligodeoxynucleotides in a mouse model of lung carcinoma. J Immunol 185(8):4641–4650

    Article  PubMed  CAS  Google Scholar 

  23. Lambrecht BN, Hammad H (2010) The role of dendritic and epithelial cells as master regulators of allergic airway inflammation. Lancet 376(9743):835–843

    Article  PubMed  CAS  Google Scholar 

  24. Sorrentino R, Morello S, Pinto A (2010) Role of plasmacytoid dendritic cells in lung-associated inflammation. Recent Pat Inflamm Allergy Drug Discov 4(2):138–143

    Article  PubMed  CAS  Google Scholar 

  25. Krieg AM (2007) Development of TLR9 agonist for cancer therapy. J Clin Invest 117(5):1184–1194

    Article  PubMed  CAS  Google Scholar 

  26. Jankowska O, Krawczyk P, Wojas-Krawczyk K, Sagan D, Milanowski J, Roliński J (2008) Phenotype of dendritic cells generated in the presence of non-small cell lung cancer antigens—preliminary report. Folia Histochem Cytobiol 46(4):465–470

    Article  PubMed  CAS  Google Scholar 

  27. Sorrentino R, Gray P, Chen S, Shimada K, Crother TR, Arditi M (2010) Plasmacytoid dendritic cells prevent cigarette smoke and Chlamydophila pneumoniae-induced Th2 inflammatory responses. Am J Respir Cell Mol Biol 43(4):422–431

    Article  PubMed  CAS  Google Scholar 

  28. Xu H, Zhang GX, Ciric B, Rostami A (2008) IDO: a double-edged sword for T(H)1/T(H)2 regulation. Immunol Lett 121(1):1–6

    Article  PubMed  CAS  Google Scholar 

  29. de Heer HJ, Hammad H, Soullié T, Hijdra D, Vos N, Willart MA, Hoogsteden HC, Lambrecht BN (2004) Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen. J Exp Med 200(1):89–98

    Article  PubMed  Google Scholar 

  30. Smit JJ, Lindell DM, Boon L, Kool M, Lambrecht BN, Lukacs NW (2008) The balance between plasmacytoid DC versus conventional DC determines pulmonary immunity to virus infections. PLoS One 3(3):e1720

    Article  PubMed  Google Scholar 

  31. Akira S, Sato S (2003) Toll-like receptors and their signaling mechanisms. Scand J Infect Dis 35(9):555–562

    Article  PubMed  CAS  Google Scholar 

  32. Smyth MJ (2005) Type I interferon and cancer immunoediting. Nature Immunol 6:646–648

    Article  CAS  Google Scholar 

  33. Fabricius D, Neubauer M, Mandel B, Schütz C, Viardot A, Vollmer A, Jahrsdörfer B, Debatin KM (2010) Prostaglandin E2 inhibits IFN-alpha secretion and Th1 costimulation by human plasmacytoid dendritic cells via E-prostanoid 2 and E-prostanoid 4 receptor engagement. J Immunol 184(2):677–684

    Article  PubMed  CAS  Google Scholar 

  34. Sharma MD, Baban B, Chandler P, Hou DY, Singh N, Yagita H, Azuma M, Blazar BR, Mellor AL, Munn DH (2007) Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2, 3-dioxygenase. J Clin Invest 117(9):2570–2582

    Article  PubMed  CAS  Google Scholar 

  35. Tokita D, Mazariegos GV, Zahorchak AF, Chien N, Abe M, Raimondi G, Thomson AW (2008) High PD-L1/CD86 ratio on plasmacytoid dendritic cells correlates with elevated T-regulatory cells in liver transplant tolerance. Transplantation 85(3):369–377

    Article  PubMed  Google Scholar 

  36. Karanikas V, Zamanakou M, Kerenidi T, Dahabreh J, Hevas A, Nakou M, Gourgoulianis KI, Germenis AE (2007) Indoleamine 2, 3-dioxygenase (IDO) expression in lung cancer. Cancer Biol Ther 6(8):1258–1262

    Article  PubMed  CAS  Google Scholar 

  37. Gregori S, Bacchetta R, Passerini L, Levings MK, Roncarolo MG (2007) Isolation, expansion, and characterization of human natural and adaptive regulatory T cells. Methods Mol Biol 380:83–105

    Article  PubMed  CAS  Google Scholar 

  38. Lee YK, Mukasa R, Hatton RD, Weaver CT (2009) Developmental plasticity of Th17 and Treg cells. Curr Opin Immunol 21(3):274–280

    Article  PubMed  CAS  Google Scholar 

  39. Gerondakis S, Grumont RJ, Banerjee A (2007) Regulating B-cell activation and survival in response to TLR signals. Immunol Cell Biol 85:471–475

    Article  PubMed  CAS  Google Scholar 

  40. Sorrentino R, Morello S, Forte G, Montinaro A, De Vita G, Luciano A, Palma G, Arra C, Maiolino P, Adcock IM, Pinto A. (2011) B Cells contribute to the anti-tumour activity of CpG-ODN in a mouse model of metastatic lung carcinoma. Am J Respir Crit Care Med

  41. Inoue S, Leitner WW, Golding B, Scott D (2006) Inhibitory effects of B cells on antitumour immunity. Cancer Res 66:7741–7747

    Article  PubMed  CAS  Google Scholar 

  42. Mantovani A, Sica A (2010) Macrophages, innate immunity and cancer: balance, tolerance, and diversity. Curr Opin Immunol 22(2):231–237

    Article  PubMed  CAS  Google Scholar 

  43. Glaros T, Larsen M, Li L (2009) Macrophages and fibroblasts during inflammation, tissue damage and organ injury. Front Biosci 14:3988–3993

    Article  PubMed  CAS  Google Scholar 

  44. Kim S, Takahashi H, Lin WW, Descargues P, Grivennikov S, Kim Y, Luo JL, Karin M (2009) Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature 457(7225):102–106

    Article  PubMed  CAS  Google Scholar 

  45. Lee CH, Wu CL, Shiau AL (2010) Toll-like receptor 4 signaling promotes tumor growth. J Immunother 33(1):73–82

    Article  PubMed  CAS  Google Scholar 

  46. Nagaraj S, Collazo M, Corzo CA, Youn JI, Ortiz M, Quiceno D, Gabrilovich DI (2009) Regulatory myeloid suppressor cells in health and disease. Cancer Res 69(19):7503–7506

    Article  PubMed  CAS  Google Scholar 

  47. Chalmin F, Ladoire S, Mignot G, Vincent J, Bruchard M, Remy-Martin JP, Boireau W, Rouleau A, Simon B, Lanneau D, De Thonel A, Multhoff G, Hamman A, Martin F, Chauffert B, Solary E, Zitvogel L, Garrido C, Ryffel B, Borg C, Apetoh L, Rébé C, Ghiringhelli F (2010) Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells. J Clin Invest 120(2):457–471

    PubMed  CAS  Google Scholar 

  48. Kalluri R, Zeisberg M (2006) Fibroblasts in cancer. Nature 6:392–401

    CAS  Google Scholar 

  49. Nahoum Rakoff, Medzhitov R (2008) Role of toll-like receptors in tissue repair and tumorigenesis. Biochemistry 73:555–561

    Google Scholar 

  50. Luo JL, Maeda S, Hsu LC, Yagita H, Karin M (2004) Inhibition of NF-kappaB in cancer cells converts inflammation- induced tumor growth mediated by TNFalpha to TRAIL-mediated tumor regression. Cancer Cell 6:297–305

    Article  PubMed  CAS  Google Scholar 

  51. Li X, Jiang S, Tapping RI (2010) Toll-like receptors signalling in cell proliferation and survival. Cytokine 49:1–9

    Article  PubMed  CAS  Google Scholar 

  52. Zitvogel L, Terme M, Borg C, Trinchieri G (2006) Dendritic cell-NK cell cross-talk: regulation and physiopathology. Curr Top Microbiol Immunol 298:157–174

    Article  PubMed  CAS  Google Scholar 

  53. Akazawa T, Masuda H, Saeki Y, Matsumoto M, Takeda K, Tsujimura K, Kuzushima K, Takahashi T, Azuma I, Akira S, Toyoshima K, Seya T (2004) Adjuvant-mediated tumor regression and tumor-specific cytotoxic response are impaired in MyD88-deficient mice. Cancer Res 64(2):757–764

    Article  PubMed  CAS  Google Scholar 

  54. Akazawa T, Ebihara T, Okuno M, Okuda Y, Shingai M, Tsujimura K, Takahashi T, Ikawa M, Okabe M, Inoue N, Okamoto-Tanaka M, Ishizaki H, Miyoshi J, Matsumoto M, Seya T (2007) Antitumor NK activation induced by the toll-like receptor 3-TICAM-1 (TRIF) pathway in myeloid dendritic cells. Proc Natl Acad Sci USA 104(1):252–257

    Article  PubMed  CAS  Google Scholar 

  55. Cheng YS, Xu F. (2010) Anticancer function of polyinosinic-polycytidylic acid. Cancer Biol Ther. 10(12)

  56. Chin AI, Miyahira AK, Covarrubias A, Teague J, Guo B, Dempsey PW, Cheng G (2010) Toll-like receptor 3-mediated suppression of TRAMP prostate cancer shows the critical role of type I interferons in tumor immune surveillance. Cancer Res 70(7):2595–2603

    Article  PubMed  CAS  Google Scholar 

  57. McCartney S, Vermi W, Gilfillan S, Cella M, Murphy TL, Schreiber RD, Murphy KM, Colonna M (2009) Distinct and complementary functions of MDA5 and TLR3 in poly(I:C)-mediated activation of mouse NK cells. J Exp Med 206(13):2967–2976

    Article  PubMed  CAS  Google Scholar 

  58. Lowe DB, Shearer MH, Aldrich JF, Winn RE, Jumper CA, Kennedy RC (2010) Role of the innate immune response and tumor immunity associated with simian virus 40 large tumor antigen. J Virol 84(19):10121–10130

    Article  PubMed  CAS  Google Scholar 

  59. Hirsch I, Caux C, Hasan U, Bendriss-Vermare N, Olive D (2010) Impaired toll-like receptor 7 and 9 signaling: from chronic viral infections to cancer. Trends Immunol 31(10):391–397

    Article  PubMed  CAS  Google Scholar 

  60. Sawahata R, Shime H, Yamazaki S, Inoue N, Akazawa T, Fujimoto Y, Fukase K, Matsumoto M, Seya T (2011) Failure of mycoplasma lipoprotein MALP-2 to induce NK cell activation through dendritic cell TLR2. Microbes Infect 13(4):350–358

    Article  PubMed  CAS  Google Scholar 

  61. Ma F, Zhang J, Zhang J, Zhang C (2010) The TLR7 agonists imiquimod and gardiquimod improve DC-based immunotherapy for melanoma in mice. Cell Mol Immunol 7(5):381–388

    Article  PubMed  CAS  Google Scholar 

  62. Zanoni I, Foti M, Ricciardi-Castagnoli P, Granucci F (2005) TLR-dependent activation stimuli associated with Th1 responses confer NK cell stimulatory capacity to mouse dendritic cells. J Immunol 175(1):286–292

    PubMed  CAS  Google Scholar 

  63. Hamm S, Rath S, Michel S, Baumgartner R (2009) Cancer immunotherapeutic potential of novel small molecule TLR7 and TLR8 agonists. J Immunotoxicol 6(4):257–265

    Article  PubMed  CAS  Google Scholar 

  64. Groot Kormelink T, Abudukelimu A, Redegeld FA (2009) Mast cells as target in cancer therapy. Curr Pharm Des 15(16):1868–1878

    Article  PubMed  CAS  Google Scholar 

  65. Tomita M, Matsuzaki Y, Onitsuka T (2000) Effect of mast cells on tumour angiogenesis in lung cancer. Am Thorac Surg 69:1686–1690

    Article  CAS  Google Scholar 

  66. Welsh TJ, Green RH, Richardson D, Waller A, O’Byrne KJ, Bradding P (2005) Macrophage and mast-cell invasion of tumor cell islets confers a marked survival advantage in non-small-cell lung cancer. J Clin Oncol 23:8959–8967

    Article  PubMed  Google Scholar 

  67. Oldford SA, Haidl ID, Howatt MA, Leiva CA, Johnston B, Marshall JS (2010) A critical role for mast cells and mast cell-derived IL-6 in TLR2-mediated inhibition of tumor growth. J Immunol 185(11):7067–7076

    Article  PubMed  CAS  Google Scholar 

  68. Tsai YG, Yang KD, Niu DM, Chien JW, Lin CY (2010) TLR2 agonists enhance CD8+Foxp3+ regulatory T cells and suppress Th2 immune responses during allergen immunotherapy. J Immunol 184(12):7229–7237

    Article  PubMed  CAS  Google Scholar 

  69. Matsushima H, Yamada N, Matsue H, Shimada S (2004) TLR3-, TLR7-, and TLR9-mediated production of proinflammatory cytokines and chemokines from murine connective tissue type skin-derived mast cells but not from bone marrow-derived mast cells. J Immunol 173(1):531–541

    PubMed  CAS  Google Scholar 

  70. Nigo YI, Yamashita M, Hirahara K, Shinnakasu R, Inami M, Kimura M, Hasegawa A, Kohno Y, Nakayama T (2006) Regulation of allergic airway inflammation through Toll-like receptor 4-mediated modification of mast cell function. Proc Natl Acad Sci USA 103(7):2286–2291

    Article  PubMed  CAS  Google Scholar 

  71. Ikeda RK, Miller M, Nayar J, Walker L, Cho JY, McElwain K, McElwain S, Raz E, Broide DH (2003) Accumulation of peribronchial mast cells in a mouse model of ovalbumin allergen induced chronic airway inflammation: modulation by immunostimulatory DNA sequences. J Immunol 171(9):4860–4867

    PubMed  CAS  Google Scholar 

  72. Kulka M, Metcalfe DD. (2006) TLR3 activation inhibits human mast cell attachment to fibronectin and vitronectin. Mol Immunol. 1579-1586

  73. Iwamura C, Nakayama T (2008) Toll-like receptors in the respiratory system: their roles in inflammation. Curr Allergy Asthma Rep 8(1):7–13

    Article  PubMed  CAS  Google Scholar 

  74. Kalluri R, Zeisberg M (2006) Fibroblasts in cancer. Nature 6:392–401

    CAS  Google Scholar 

  75. Damiano V, Caputo R, Garofalo S, Bianco R, Rosa R, Merola G, Gelardi T, Racioppi L, Fontanini G, De Placido S, Kandimalla ER, Agrawal S, Ciardiello F, Tortora G (2007) TLR9 agonist acts by different mechanisms synergizing with bevacizumab in sensitive and cetuximab-resistant colon cancer xenografts. Proc Natl Acad Sci USA 104(30):12468–12473

    Article  PubMed  CAS  Google Scholar 

  76. Droemann D, Albrecht D, Gerdes J, Ulmer AJ, Branscheid D, Vollmer E, Dalhoff K, Zabel P, Goldmann T (2005) Human lung cancer cells express functionally active Toll-like receptor 9. Respir Res 6:1

    Article  PubMed  Google Scholar 

  77. Wenzel J, Uerlich M, Haller O, Bieber T, Tueting T (2005) Enhanced type I interferon signaling and recruitment of chemokine receptor CXCR3-expressing lymphocytes into the skin following treatment with the TLR7-agonist imiquimod. J Cutan Pathol 32(4):257–262

    Article  PubMed  Google Scholar 

  78. Johnson B, Osada T, Clay T, Lyerly H, Morse M (2009) Physiology and therapeutics of vascular endothelial growth factor in tumor immunosuppression. Curr Mol Med 9(6):702–707

    Article  PubMed  CAS  Google Scholar 

  79. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306–1309

    Article  PubMed  CAS  Google Scholar 

  80. Sorrentino R, Morello S, Giordano MG, Arra C, Maiolino P, Adcock IM, Pinto A (2011) CpG-ODN increases the release of VEGF in a mouse model of lung carcinoma. Int J Cancer 128(12):2815–2822

    Article  PubMed  CAS  Google Scholar 

  81. Chapoval SP, Lee CG, Tang C, Keegan AD, Cohn L, Bottomly K, Elias JA (2009) Lung vascular endothelial growth factor expression induces local myeloid dendritic cell activation. Clin Immunol 132(3):371–384

    Article  PubMed  CAS  Google Scholar 

  82. Elenbaas B, Weinberg RA (2001) Heterotypic signalling between epithelial tumour cells and fibroblasts in carcinoma formation. Exp Cell Res 264(1):169–184

    Article  PubMed  CAS  Google Scholar 

  83. Li J, Ma Z, Tang ZL, Stevens T, Pitt B, Li S (2004) CpG DNA-mediated immune response in pulmonary endothelial cells. Am J Physiol Lung Cell Mol Physiol 287(3):L552–L558

    Article  PubMed  CAS  Google Scholar 

  84. Bedke T, Pretsch L, Karakhanova S, Enk AH, Mahnke K (2010) Endothelial cells augment the suppressive function of CD4+ CD25+ Foxp3+ regulatory T cells: involvement of programmed death-1 and IL-10. J Immunol 184(10):5562–5570

    Article  PubMed  CAS  Google Scholar 

  85. Engelhardt R, Otto F, Mackensen A, Mertelsmann R, Galanos C (1995) Endotoxin (Salmonella abortus equi) in cancer patients Clinical and immunological findings. Prog Clin Biol Res 392:253–261

    PubMed  CAS  Google Scholar 

  86. Liu C, Lou Y, Lizée G, Qin H, Liu S, Rabinovich B, Kim GJ, Wang YH, Ye Y, Sikora AG, Overwijk WW, Liu YJ, Wang G, Hwu P (2008) Plasmacytoid dendritic cells induce NK cell-dependent, tumor antigen-specific T cell cross-priming and tumor regression in mice. J Clin Invest 118(3):1165–1175

    PubMed  CAS  Google Scholar 

  87. Luo JL, Maeda S, Hsu LC, Yagita H, Karin M (2004) Inhibition of NF-kappaB in cancer cells converts inflammation- induced tumor growth mediated by TNFalpha to TRAIL-mediated tumor regression. Cancer Cell 6:297–305

    Article  PubMed  CAS  Google Scholar 

  88. Li X, Jiang S, Tapping RI (2010) Toll-like receptors signalling in cell proliferation and survival. Cytokine 49:1–9

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank Dr. Giovanni Forte and Dr.Pearl Gray, who critically read our manuscript. We are thankful to the University of Salerno for providing the financial support (FARB) for current research. Dr. Rosalinda Sorrentino is supported by the University of Salerno Fellowship.

Author information

Authors and Affiliations

  1. Pharmaceutical and Biomedical Sciences Department (FARMABIOMED), University of Salerno, 84084, Fisciano, Salerno, Italy

    Aldo Pinto, Silvana Morello & Rosalinda Sorrentino

Authors
  1. Aldo Pinto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Silvana Morello
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rosalinda Sorrentino
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rosalinda Sorrentino.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pinto, A., Morello, S. & Sorrentino, R. Lung cancer and Toll-like receptors. Cancer Immunol Immunother 60, 1211–1220 (2011). https://doi.org/10.1007/s00262-011-1057-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-011-1057-8

Keywords

Search

Navigation