A “Toll Bridge” for Tumor-Specific T Cells

Chapter

Abstract

Toll-like receptors are among the fundamental molecules that alert the immune system to the presence of an infection by recognizing pathogen-associated molecules. The engagement of TLRs results in the activation of the adaptive immune system and the production of inflammatory molecules and various chemokines. Much of our understanding regarding TLR function stems from the study of innate immune cells, such as dendritic cells and macrophages. However, emerging studies from various groups, including ours, have shown that TLRs are expressed on CD4+ and CD8+ T cells and can function as costimulatory molecules. The engagement of TLRs on various T cell subsets enhances cell survival, proliferation, and/or increases the production of cytokines and effector molecules. These findings reveal a novel role for TLR agonists and may inspire new approaches in the development of immunotherapies and vaccines that are more effective by targeting or manipulating TLR signaling within T cells.

Keywords

Migration Arthritis Tyrosine Leukemia Sarcoma 

Notes

Acknowledgments

This work was supported by a National Institutes of Health (NIH) Center for Biomedical Research Excellence Grant (1P20RR021970) and the Louisiana Cancer Research Consortium NIH grant number 1R01CA140917–0109 as a source of support.

References

  1. 1.
    Coley, W. B. (1893) Clin Orthop Relat Res 1991, 3Google Scholar
  2. 2.
    Akira, S., and Hemmi, H. (2003) Immunol Lett 85, 85CrossRefPubMedGoogle Scholar
  3. 3.
    Iwasaki, A., and Medzhitov, R. (2004) 5, 987Google Scholar
  4. 4.
    Ghosh, T. K., Mickelson, D. J., Fink, J., Solberg, J. C., Inglefield, J. R., Hook, D., Gupta, S. K., Gibson, S., and Alkan, S. S. (2006) Cell Immunol 243, 48CrossRefPubMedGoogle Scholar
  5. 5.
    Prins, R. M., Craft, N., Bruhn, K. W., Khan-Farooqi, H., Koya, R. C., Stripecke, R., Miller, J. F., and Liau, L. M. (2006) J. Immunol 176, 157PubMedGoogle Scholar
  6. 6.
    Masopust, D., Kaech, S. M., Wherry, E. J., and Ahmed, R. (2004) Curr Opin Immunol 16, 217CrossRefPubMedGoogle Scholar
  7. 7.
    Russell, J. H., White, C. L., Loh, D. Y., and Meleedy-Rey, P. (1991) Proc Natl Acad Sci USA 88, 2151CrossRefPubMedGoogle Scholar
  8. 8.
    Russell, J. H. (1995) Curr Opin Immunol 7, 388Google Scholar
  9. 9.
    Sprent, J., and Tough, D. F. (1994) Lymphocyte life-span and memory. Science 265, 1395CrossRefPubMedGoogle Scholar
  10. 10.
    Sallusto, F., Geginat, J., and Lanzavecchia, A. (2004) Annu Rev Immunol 22, 745CrossRefPubMedGoogle Scholar
  11. 11.
    Babu, S., Blauvelt, C. P., Kumaraswami, V., and Nutman, T. B. (2006) J Immunol 176, 3885PubMedGoogle Scholar
  12. 12.
    Crellin, N. K., Garcia, R. V., Hadisfar, O., Allan, S. E., Steiner, T. S., and Levings, M. K. (2005) J Immunol 175, 8051PubMedGoogle Scholar
  13. 13.
    Komai-Koma, M., Jones, L., Ogg, G. S., Xu, D., and Liew, F. Y. (2004) Proc Natl Acad Sci USA 101, 3029CrossRefPubMedGoogle Scholar
  14. 14.
    Mansson, A., Adner, M., and Cardell, L. O. (2006) Respir Res 7, 36CrossRefPubMedGoogle Scholar
  15. 15.
    Wesch, D., Beetz, S., Oberg, H. H., Marget, M., Krengel, K., and Kabelitz, D. (2006) J Immunol 176, 1348PubMedGoogle Scholar
  16. 16.
    Asprodites, N., Zheng, L., Geng, D., Velasco-Gonzalez, C., Sanchez-Perez, L., and Davila, E. (2008) FASEB J in pressGoogle Scholar
  17. 17.
    Cottalorda, A., Verschelde, C., Marcais, A., Tomkowiak, M., Musette, P., Uematsu, S., Akira, S., Marvel, J., and Bonnefoy-Berard, N. (2006) Eur J Immunol 36, 1684CrossRefPubMedGoogle Scholar
  18. 18.
    Sobek, V., Birkner, N., Falk, I., Wurch, A., Kirschning, C. J., Wagner, H., Wallich, R., Lamers, M. C., and Simon, M. M. (2004) Arthritis Res Ther 6, R433CrossRefPubMedGoogle Scholar
  19. 19.
    Raffeiner, B., Dejaco, C., Duftner, C., Kullich, W., Goldberger, C., Vega, S. C., Keller, M., Grubeck-Loebenstein, B., and Schirmer, M. (2005) Arthritis Res Ther 7, R1412CrossRefPubMedGoogle Scholar
  20. 20.
    Peng, G., Guo, Z., Kiniwa, Y., Voo, K. S., Peng, W., Fu, T., Wang, D. Y., Li, Y., Wang, H. Y., and Wang, R. F. (2005) Science 309, 1380CrossRefPubMedGoogle Scholar
  21. 21.
    Bendigs, S., Salzer, U., Lipford, G. B., Wagner, H., and Heeg, K. (1999) Eur J Immunol 29, 1209CrossRefPubMedGoogle Scholar
  22. 22.
    Caron, G., Duluc, D., Fremaux, I., Jeannin, P., David, C., Gascan, H., and Delneste, Y. (20050 J Immunol 175, 1551Google Scholar
  23. 23.
    Matsuguchi, T., Takagi, K., Musikacharoen, T., and Yoshikai, Y. (2000) Blood 95, 1378PubMedGoogle Scholar
  24. 24.
    Greil, R., Anether, G., Johrer, K., and Tinhofer, I. (2003) J Leukoc Biol 74, 311CrossRefPubMedGoogle Scholar
  25. 25.
    Tschopp, J., Irmler, M., and Thome, M. (1998) Curr Opin Immunol 10, 552CrossRefPubMedGoogle Scholar
  26. 26.
    Davila, E., Velez, M. G., Heppelmann, C. J., and Celis, E. (2002) Blood 100, 2537CrossRefPubMedGoogle Scholar
  27. 27.
    Chao, D. T. and Korsmeyer, S. J. (1998) Annu Rev Immunol 16, 395CrossRefPubMedGoogle Scholar
  28. 28.
    Charo, J., Finkelstein, S. E., Grewal, N., Restifo, N. P., Robbins, P. F., and Rosenberg, S. A. (2005) Cancer Res 65, 2001CrossRefPubMedGoogle Scholar
  29. 29.
    Gelman, A. E., Zhang, J., Choi, Y., and Turka, L. A. (2004) J Immunol 172, 6065PubMedGoogle Scholar
  30. 30.
    Gelman, A. E., LaRosa, D. F., Zhang, J., Walsh, P. T., Choi, Y., Sunyer, J. O., and Turka, L. A. (2006) Immunity 25, 783CrossRefPubMedGoogle Scholar
  31. 31.
    Zheng, L., Asprodites, N., Keene, A. H., Rodriguez, P., Brown, K. D., and Davila, E. (2008) Blood 111, 2704CrossRefPubMedGoogle Scholar
  32. 32.
    Glimcher, L. H., Townsend, M. J., Sullivan, B. M., and Lord, G. M. (2004) Nat Rev Immunol 4, 900CrossRefPubMedGoogle Scholar
  33. 33.
    Kabelitz, D. (2007) Curr Opin Immunol 19, 39CrossRefPubMedGoogle Scholar
  34. 34.
    Pearce, E. L., Mullen, A. C., Martins, G. A., Krawczyk, C. M., Hutchins, A. S., Zediak, V. P., Banica, M., DiCioccio, C. B., Gross, D. A., Mao, C. A., Shen, H., Cereb, N., Yang, S. Y., Lindsten, T., Rossant, J., Hunter, C. A., and Reiner, S. L. (2003) Science 302, 1041CrossRefPubMedGoogle Scholar
  35. 35.
    Intlekofer, A. M., Takemoto, N., Wherry, E. J., Longworth, S. A., Northrup, J. T., Palanivel, V. R., Mullen, A. C., Gasink, C. R., Kaech, S. M., Miller, J. D., Gapin, L., Ryan, K., Russ, A. P., Lindsten, T., Orange, J. S., Goldrath, A. W., Ahmed, R., and Reiner, S. L. (2005) Nat Immunol 6, 1236CrossRefPubMedGoogle Scholar
  36. 36.
    Sullivan, B. M., Juedes, A., Szabo, S. J., von, H. M., and Glimcher, L. H. (2003) Proc Natl Acad Sci USA 100, 15818CrossRefPubMedGoogle Scholar
  37. 37.
    Mokuno, Y., Matsuguchi, T., Takano, M., Nishimura, H., Washizu, J., Ogawa, T., Takeuchi, O., Akira, S., Nimura, Y., and Yoshikai, Y. (2000) J Immunol 165, 931PubMedGoogle Scholar
  38. 38.
    Schwarz, K., Storni, T., Manolova, V., Didierlaurent, A., Sirard, J. C., Rothlisberger, P., and Bachmann, M. F. (2003) Eur J Immunol 33, 1465CrossRefPubMedGoogle Scholar
  39. 39.
    Lighvani, A. A., Frucht, D. M., Jankovic, D., Yamane, H., Aliberti, J., Hissong, B. D., Nguyen, B. V., Gadina, M., Sher, A., Paul, W. E., and O’Shea, J. J. (2001) Proc Natl Acad Sci USA 98, 15137CrossRefPubMedGoogle Scholar
  40. 40.
    Lugo-Villarino, G., Ito, S., Klinman, D. M., and Glimcher, L. H. (2005) Proc Natl Acad Sci USA 102, 13248CrossRefPubMedGoogle Scholar
  41. 41.
    Farber, D. L. (1998) J Immunol 160, 535PubMedGoogle Scholar
  42. 42.
    Masopust, D., and Ahmed, R. (2004) Immunol Res 29, 151CrossRefPubMedGoogle Scholar
  43. 43.
    Opferman, J. T., Ober, B. T., and shton-Rickardt, P. G. (1999) Science 283, 1745CrossRefPubMedGoogle Scholar
  44. 44.
    Van Stipdonk, M. J., Lemmens, E. E., and Schoenberger, S. P. (2001) Nat Immunol 2, 423PubMedGoogle Scholar
  45. 45.
    Van Stipdonk, M. J., Hardenberg, G., Bijker, M. S., Lemmens, E. E., Droin, N. M., Green, D. R., and Schoenberger, S. P. (2003) Nat Immunol 4, 361CrossRefPubMedGoogle Scholar
  46. 46.
    Pasare, C., and Medzhitov, R. (2004) Immunity 21, 733CrossRefPubMedGoogle Scholar
  47. 47.
    Zanin-Zhorov, A., Nussbaum, G., Franitza, S., Cohen, I. R., and Lider, O. (2003) FASEB J 17, 1567PubMedGoogle Scholar
  48. 48.
    Fan, J., and Malik, A. B. (2003) Nat Med 9, 315CrossRefPubMedGoogle Scholar
  49. 49.
    Masopust, D., Vezys, V., Marzo, A. L., and Lefrancois, L. (2001) Science 291, 2413CrossRefPubMedGoogle Scholar
  50. 50.
    Curiel, T. J. (2007) J Clin Invest 117, 1167CrossRefPubMedGoogle Scholar
  51. 51.
    Curotto de Lafaille, M. A., and Lafaille, J. J. (2002) Curr Opin Immunol 14, 771CrossRefPubMedGoogle Scholar
  52. 52.
    Lanzavecchia, A., and Sallusto, F. (2001) Cell 106, 263CrossRefPubMedGoogle Scholar
  53. 53.
    Sutmuller, R. P., den Brok, M. H., Kramer, M., Bennink, E. J., Toonen, L. W., Kullberg, B. J., Joosten, L. A., Akira, S., Netea, M. G., and Adema, G. J. (2006) J Clin Invest 116, 485CrossRefPubMedGoogle Scholar
  54. 54.
    Casares, N., Arribillaga, L., Sarobe, P., Dotor, J., Lopez-Diaz de, C. A., Melero, I., Prieto, J., Borras-Cuesta, F., and Lasarte, J. J. (2003) J Immunol 171, 5931PubMedGoogle Scholar
  55. 55.
    Morse, M. A., Hobeika, A. C., Osada, T., Serra, D., Niedzwiecki, D., Lyerly, H. K., and Clay, T. M. (2008) Blood 112, 610CrossRefPubMedGoogle Scholar
  56. 56.
    Liu, H., Komai-Koma, M., Xu, D., and Liew, F. Y. (2006) Proc Natl Acad Sci USA 103, 7048CrossRefPubMedGoogle Scholar
  57. 57.
    Caramalho, I., Lopes-Carvalho, T., Ostler, D., Zelenay, S., Haury, M., and Demengeot, J. (2003) J Exp Med 197, 403CrossRefPubMedGoogle Scholar
  58. 58.
    LaRosa, D. F., Stumhofer, J. S., Gelman, A. E., Rahman, A. H., Taylor, D. K., Hunter, C. A., and Turka, L. A. (2008) Proc Natl Acad Sci USA 105, 3855CrossRefPubMedGoogle Scholar
  59. 59.
    van der Heijden, I., Wilbrink, B., Tchetverikov, I., Schrijver, I. A., Schouls, L. M., Hazenberg, M. P., Breedveld, F. C., and Tak, P. P. (2000) Arthritis Rheum 43, 593CrossRefPubMedGoogle Scholar
  60. 60.
    Ronaghy, A., Prakken, B. J., Takabayashi, K., Firestein, G. S., Boyle, D., Zvailfler, N. J., Roord, S. T., Albani, S., Carson, D. A., and Raz, E. (2002) J Immunol 168, 51PubMedGoogle Scholar
  61. 61.
    Meng, Y., Carpentier, A. F., Chen, L., Boisserie, G., Simon, J. M., Mazeron, J. J., and Delattre, J. Y. (2005) Int J Cancer 116, 992CrossRefPubMedGoogle Scholar
  62. 62.
    Mason, K. A., Ariga, H., Neal, R., Valdecanas, D., Hunter, N., Krieg, A. M., Whisnant, J. K., and Milas, L. (2005) Clin Cancer Res 11, 361PubMedGoogle Scholar
  63. 63.
    Mason, K. A., Neal, R., Hunter, N., Ariga, H., Ang, K., and Milas, L. (2006) Radiother Oncol 80, 192CrossRefPubMedGoogle Scholar
  64. 64.
    Larsson, M., Fonteneau, J. F., and Bhardwaj, N. (2001) Trends Immunol 22, 141CrossRefPubMedGoogle Scholar
  65. 65.
    Klein, H., Mehlhorn, H., and Ruger, W. (1996) Parasitol Res 82, 468CrossRefPubMedGoogle Scholar
  66. 66.
    Sheard, M. A., Vojtesek, B., Janakova, L., Kovarik, J., and Zaloudik, J. (1997) Int J Cancer 73, 757CrossRefPubMedGoogle Scholar
  67. 67.
    Sheard, M. A. (2001) Int J Cancer 96, 213CrossRefPubMedGoogle Scholar
  68. 68.
    Chakraborty, M., Abrams, S. I., Camphausen, K., Liu, K., Scott, T., Coleman, C. N., and Hodge, J. W. (2003) J Immunol 170, 6338PubMedGoogle Scholar
  69. 69.
    Garnett, C. T., Palena, C., Chakraborty, M., Tsang, K. Y., Schlom, J., and Hodge, J. W. (2004) Cancer Res 64, 7985CrossRefPubMedGoogle Scholar
  70. 70.
    Cho, B. K., Rao, V. P., Ge, Q., Eisen, H. N., and Chen, J. (2000) J Exp Med 192, 549CrossRefPubMedGoogle Scholar
  71. 71.
    Ge, Q., Palliser, D., Eisen, H. N., and Chen, J. (2002) Proc Natl Acad Sci USA 99, 2983CrossRefPubMedGoogle Scholar
  72. 72.
    Goldrath, A. W., Bogatzki, L. Y., and Bevan, M. J. (2000) J Exp Med 192, 557CrossRefPubMedGoogle Scholar
  73. 73.
    Dudley, M. E., Wunderlich, J. R., Robbins, P. F., Yang, J. C., Hwu, P., Schwartzentruber, D. J., Topalian, S. L., Sherry, R., Restifo, N. P., Hubicki, A. M., Robinson, M. R., Raffeld, M., Duray, P., Seipp, C. A., Rogers-Freezer, L., Morton, K. E., Mavroukakis, S. A., White, D. E., and Rosenberg, S. A. (2002) Science 298, 850CrossRefPubMedGoogle Scholar
  74. 74.
    Dummer, W., Ernst, B., LeRoy, E., Lee, D., and Surh, C. (2001) J Immunol 166, 2460PubMedGoogle Scholar
  75. 75.
    Dummer, W., Niethammer, A. G., Baccala, R., Lawson, B. R., Wagner, N., Reisfeld, R. A., and Theofilopoulos, A. N. (2002) J Clin Invest 110, 185PubMedGoogle Scholar
  76. 76.
    Hellstrom, K. E. and Hellstrom, I. (1978) Proc Natl Acad Sci USA 75, 436CrossRefPubMedGoogle Scholar
  77. 77.
    Hellstrom, K. E., Hellstrom, I., Kant, J. A., and Tamerius, J. D. (1978) J Exp Med 148, 799CrossRefPubMedGoogle Scholar
  78. 78.
    Hu, H. M., Poehlein, C. H., Urba, W. J., and Fox, B. A. (2002) Cancer Res 62, 3914PubMedGoogle Scholar
  79. 79.
    Bohnhorst, J., Rasmussen, T., Moen, S. H., Flottum, M., Knudsen, L., Borset, M., Espevik, T., and Sundan, A. (2006) Leukemia 20, 1138CrossRefPubMedGoogle Scholar
  80. 80.
    Jozsef, L., Khreiss, T., and Filep, J. G. (2004) FASEB J 18, 1776PubMedGoogle Scholar
  81. 81.
    Kuo, C. C., Liang, S. M., and Liang, C. M. (2006) J Biol Chem 281, 38200CrossRefPubMedGoogle Scholar
  82. 82.
    Sester, D. P., Brion, K., Trieu, A., Goodridge, H. S., Roberts, T. L., Dunn, J., Hume, D. A., Stacey, K. J., and Sweet, M. J. (2006) J Immunol 177, 4473PubMedGoogle Scholar
  83. 83.
    Sohn, W. J., Lee, K. W., Choi, S. Y., Chung, E., Lee, Y., Kim, T. Y., Lee, S. K., Choe, Y. K., Lee, J. H., Kim, D. S., and Kwon, H. J. (2006) Mol Immunol 43, 1163CrossRefPubMedGoogle Scholar
  84. 84.
    Yi, A. K., Chang, M., Peckham, D. W., Krieg, A. M., and Ashman, R. F. (1998) J Immunol 160, 5898PubMedGoogle Scholar
  85. 85.
    Yi, A. K., Peckham, D. W., Ashman, R. F., and Krieg, A. M. (1999) Int Immunol 11, 2015CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Pediatrics and the Stanley S. Scott Cancer CenterLouisiana State University Health Sciences CenterNew OrleansUSA

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