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The Role of Natural Killer T cells in Tumor Immunity

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References

  1. Sogn, J.A. 1998. Tumor immunology: the glass is half full. Immunity 9:757–763

    Article  PubMed  CAS  Google Scholar 

  2. Blattman, J.N., and P.D. Greenberg. 2004. Cancer Immunotherapy: A treatment for the masses. Science 305:200–205

    Article  PubMed  CAS  Google Scholar 

  3. Bendelac, A., M.N. Rivera, S.H. Park, and J.H. Roark. 1997. Mouse CD1-specific NK1 T cells: development, specificity, and function. Annu Rev Immunol 15:535–562

    Article  PubMed  CAS  Google Scholar 

  4. Godfrey, D.I., H.R. MacDonald, M. Kronenberg, M.J. Smyth, and L. Van Kaer. 2004. NKT cells: what’s in a name? Nat Rev Immunol 4:231–237

    Article  PubMed  CAS  Google Scholar 

  5. Godfrey, D.I., and M. Kronenberg. 2004. Going both ways: Immune regulation via CD1d-dependent NKT cells. J Clin Invest 114:1379–1388

    Article  PubMed  CAS  Google Scholar 

  6. Kronenberg, M. 2005. Toward an understanding of NKT cell biology: progress and paradoxes. Annu Rev Immunol 23:877–900

    Article  PubMed  CAS  Google Scholar 

  7. Brigl, M., and M.B. Brenner. 2004. CD1: antigen presentation and T cell function. Annu Rev Immunol 22:817–890

    Article  PubMed  CAS  Google Scholar 

  8. Dellabona, P., E. Padovan, G. Casorati, M. Brockhaus, and A. Lanzavecchia. 1994. An invariant V alpha 24-J alpha Q/V beta 11 T cell receptor is expressed in all individuals by clonally expanded CD4–8- T cells. J Exp Med 180:1171–1176

    Article  PubMed  CAS  Google Scholar 

  9. Gadola, S.D., N. Dulphy, M. Salio, and V. Cerundolo. 2002. Valpha24-JalphaQ-independent, CD1d-restricted recognition of alpha-galactosylceramide by human CD4(+) and CD8alphabeta(+) T lymphocytes. J Immunol 168:5514–5520

    PubMed  CAS  Google Scholar 

  10. Slifka, M.K., R.R. Pagarigan, and J.L. Whitton. 2000. NK markers are expressed on a high percentage of virus-specific CD8+ and CD4+ T cells [published erratum appears in J Immunol 2000 Mar 15;164(6):following 3444]. J Immunol 164:2009–2015

    PubMed  CAS  Google Scholar 

  11. Gumperz, J.E., C. Roy, A. Makowska, D. Lum, M. Sugita, T. Podrebarac, Y. Koezuka, S.A. Porcelli, S. Cardell, M.B. Brenner, and S.M. Behar. 2000. Murine CD1d-restricted T cell recognition of cellular lipids. Immunity 12:211–221

    Article  PubMed  CAS  Google Scholar 

  12. Hayakawa, Y., D.I. Godfrey, and M.J. Smyth. 2004. Alpha-galactosylceramide: potential immunomodulatory activity and future application. Curr Med Chem 11:241–252

    Article  PubMed  CAS  Google Scholar 

  13. Sidobre, S., O.V. Naidenko, B.C. Sim, N.R. Gascoigne, K.C. Garcia, and M. Kronenberg. 2002. The V alpha 14 NKT cell TCR exhibits high-affinity binding to a glycolipid/CD1d complex. J Immunol 169:1340–1348

    PubMed  CAS  Google Scholar 

  14. Wu, D.Y., N.H. Segal, S. Sidobre, M. Kronenberg, and P.B. Chapman. 2003. Cross-presentation of disialoganglioside GD3 to natural killer T cells. J Exp Med 198:173–181

    Article  PubMed  CAS  Google Scholar 

  15. Schofield, L., M.J. McConville, D. Hansen, A.S. Campbell, B. Fraser-Reid, M.J. Grusby, and S.D. Tachado. 1999. CD1d-restricted immunoglobulin G formation to GPI-anchored antigens mediated by NKT cells. Science 283:225–229

    Article  PubMed  CAS  Google Scholar 

  16. Rauch, J., J. Gumperz, C. Robinson, M. Skold, C. Roy, D.C. Young, M. Lafleur, D.B. Moody, M.B. Brenner, C.E. Costello, and S.M. Behar. 2003. Structural features of the acyl chain determine self-phospholipid antigen recognition by a CD1d-restricted invariant NKT (iNKT) cell. J Biol Chem 278:47508–47515

    Article  PubMed  CAS  Google Scholar 

  17. Ortaldo, J.R., H.A. Young, R.T. Winkler-Pickett, E.W. Bere, Jr., W.J. Murphy, and R.H. Wiltrout. 2004. Dissociation of NKT stimulation, cytokine induction, and NK activation in vivo by the use of distinct TCR-binding ceramides. J Immunol 172:943–953

    PubMed  CAS  Google Scholar 

  18. Zhou, D., J. Mattner, C. Cantu, 3rd, N. Schrantz, N. Yin, Y. Gao, Y. Sagiv, K. Hudspeth, Y.P. Wu, T. Yamashita, S. Teneberg, D. Wang, R.L. Proia, S.B. Levery, P.B. Savage, L. Teyton, and A. Bendelac. 2004. Lysosomal glycosphingolipid recognition by NKT cells. Sciencebreak 306:1786–1789

    CAS  Google Scholar 

  19. Mattner, J., K.L. Debord, N. Ismail, R.D. Goff, C. Cantu, 3rd, D. Zhou, P. Saint-Mezard, V. Wang, Y. Gao, N. Yin, K. Hoebe, O. Schneewind, D. Walker, B. Beutler, L. Teyton, P.B. Savage, and A. Bendelac. 2005. Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature 434:525–529

    Article  PubMed  CAS  Google Scholar 

  20. Kinjo, Y., D. Wu, G. Kim, G.W. Xing, M.A. Poles, D.D. Ho, M. Tsuji, K. Kawahara, C.H. Wong, and M. Kronenberg. 2005. Recognition of bacterial glycosphingolipids by natural killer T cells. Nature 434:520–525

    Article  PubMed  CAS  Google Scholar 

  21. Wu, D., G.W. Xing, M.A. Poles, A. Horowitz, Y. Kinjo, B. Sullivan, V. Bodmer-Narkevitch, O. Plettenburg, M. Kronenberg, M. Tsuji, D.D. Ho, and C.H. Wong. 2005. Bacterial glycolipids and analogs as antigens for CD1d-restricted NKT cells. Proc Natl Acad Sci U S A 102:1351–1356

    Google Scholar 

  22. Moody, D.B., D.C. Young, T.Y. Cheng, J.P. Rosat, C. Roura-Mir, P.B. O’Connor, D.M. Zajonc, A. Walz, M.J. Miller, S.B. Levery, I.A. Wilson, C.E. Costello, and M.B. Brenner. 2004. T cell activation by lipopeptide antigens. Science 303:527–531

    Article  PubMed  CAS  Google Scholar 

  23. Matsuda, J.L., L. Gapin, J.L. Baron, S. Sidobre, D.B. Stetson, M. Mohrs, R.M. Locksley, and M. Kronenberg. 2003. Mouse V alpha 14i natural killer T cells are resistant to cytokine polarization in vivo. Proc Natl Acad Sci U S A 100:8395–8400

    Google Scholar 

  24. Stetson, D.B., M. Mohrs, R.L. Reinhardt, J.L. Baron, Z.E. Wang, L. Gapin, M. Kronenberg, and R.M. Locksley. 2003. Constitutive cytokine mRNAs mark natural killer (NK) and NK T cells poised for rapid effector function. J Exp Med 198:1069–1076

    Article  PubMed  CAS  Google Scholar 

  25. Carnaud, C., D. Lee, O. Donnars, S.H. Park, A. Beavis, Y. Koezuka, and A. Bendelac. 1999. Cutting edge: Cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells. J Immunol 163:4647–4650

    PubMed  CAS  Google Scholar 

  26. Eberl, G., and H.R. MacDonald. 2000. Selective induction of NK cell proliferation and cytotoxicity by activated NKT cells. Eur J Immunol 30:985–992

    Article  PubMed  CAS  Google Scholar 

  27. Vincent, M.S., D.S. Leslie, J.E. Gumperz, X. Xiong, E.P. Grant, and M.B. Brenner. 2002. CD1-dependent dendritic cell instruction. Nat Immunol 3:1163–1168

    Article  PubMed  CAS  Google Scholar 

  28. Smyth, M.J., N.Y. Crowe, D.G. Pellicci, K. Kyparissoudis, J.M. Kelly, K. Takeda, H. Yagita, and D.I. Godfrey. 2002. Sequential production of interferon-gamma by NK1. 1(+) T cells and natural killer cells is essential for the antimetastatic effect of alpha-galactosylceramide. Blood 99:h1259–1266.

    Google Scholar 

  29. Galli, G., S. Nuti, S. Tavarini, L. Galli-Stampino, C. De Lalla, G. Casorati, P. Dellabona, and S. Abrignani. 2003. CD1d-restricted Help To B Cells By Human Invariant Natural Killer T Lymphocytes. J Exp Med 197:1051–1057

    Article  PubMed  CAS  Google Scholar 

  30. Hermans, I.F., J.D. Silk, U. Gileadi, M. Salio, B. Mathew, G. Ritter, R. Schmidt, A.L. Harris, L. Old, and V. Cerundolo. 2003. NKT cells enhance CD4+ and CD8+ T cell responses to soluble antigen in vivo through direct interaction with dendritic cells. J Immunol 171:5140–5147

    PubMed  CAS  Google Scholar 

  31. Fujii, S., K. Shimizu, C. Smith, L. Bonifaz, and R.M. Steinman. 2003. Activation of natural killer T cells by alpha-galactosylceramide rapidly induces the full maturation of dendritic cells in vivo and thereby acts as an adjuvant for combined CD4 and CD8 T cell immunity to a coadministered protein. J Exp Med 198:267–279

    Article  PubMed  CAS  Google Scholar 

  32. Fujii, S., K. Liu, C. Smith, A.J. Bonito, and R.M. Steinman. 2004. The linkage of innate to adaptive immunity via maturing dendritic cells in vivo requires CD40 ligation in addition to antigen presentation and CD80/86 costimulation. J Exp Med 199:1607–1618

    Article  PubMed  CAS  Google Scholar 

  33. Chen, Y.G., C.M. Choisy-Rossi, T.M. Holl, H.D. Chapman, G.S. Besra, S.A. Porcelli, D.J. Shaffer, D. Roopenian, S.B. Wilson, and D.V. Serreze. 2005. Activated NKT cells inhibit autoimmune diabetes through tolerogenic recruitment of dendritic cells to pancreatic lymph nodes. J Immunol 174:1196–1204

    PubMed  CAS  Google Scholar 

  34. Gumperz, J.E., S. Miyake, T. Yamamura, and M.B. Brenner. 2002. Functionally distinct subsets of CD1d-restricted natural killer T cells revealed by CD1d tetramer staining. J Exp Med 195:625–636

    Article  PubMed  CAS  Google Scholar 

  35. Lee, P.T., K. Benlagha, L. Teyton, and A. Bendelac. 2002. Distinct functional lineages of human V(alpha)24 natural killer T cells. J Exp Med 195:637–641

    Article  PubMed  CAS  Google Scholar 

  36. Smyth, M.J., N.Y. Crowe, Y. Hayakawa, K. Takeda, H. Yagita, and D.I. Godfrey. 2002. NKT cells - conductors of tumor immunity? Curr Opin Immunol 14:165–171

    Article  PubMed  CAS  Google Scholar 

  37. Smyth, M.J., and D.I. Godfrey. 2000. NKT cells and tumor immunity–a double-edged sword. Nat Immunol 1:459–460

    Article  PubMed  CAS  Google Scholar 

  38. Wilson, S.B., and T.L. Delovitch. 2003. Janus-like role of regulatory iNKT cells in autoimmune disease and tumour immunity. Nat Rev Immunol 3:211–222

    Article  PubMed  CAS  Google Scholar 

  39. Cui, J., T. Shin, T. Kawano, H. Sato, E. Kondo, I. Toura, Y. Kaneko, H. Koseki, M. Kanno, and M. Taniguchi. 1997. Requirement for Va 14 NKT cells by glycosylceramides. Science 278: 1623–1626.

    Article  PubMed  CAS  Google Scholar 

  40. Kawano, T., T. Nakayama, N. Kamada, Y. Kaneko, M. Harada, N. Ogura, Y. Akutsu, S. Motohashi, T. Iizasa, H. Endo, T. Fujisawa, H. Shinkai, and M. Taniguchi. 1999. Antitumor cytotoxicity mediated by ligand-activated human V alpha24 NKT cells. Cancer Res 59:5102–5105

    PubMed  CAS  Google Scholar 

  41. Hayakawa, Y., S. Rovero, G. Forni, and M.J. Smyth. 2003. Alpha-galactosylceramide (KRN7000) suppression of chemical- and oncogene-dependent carcinogenesis. Proc Natl Acad Sci USA 100:9464–9469

    Article  PubMed  CAS  Google Scholar 

  42. Hayakawa, Y., K. Takeda, H. Yagita, S. Kakuta, Y. Iwakura, L. Van Kaer, I. Saiki, and K. Okumura. 2001. Critical contribution of IFN-gamma and NK cells, but not perforin-mediated cytotoxicity, to anti-metastatic effect of alpha-galactosylceramide. Eur J Immunol 31:1720–1727

    Article  PubMed  CAS  Google Scholar 

  43. Hayakawa, Y., K. Takeda, H. Yagita, M.J. Smyth, L. Van Kaer, K. Okumura, and I. Saiki. 2002. IFN-gamma-mediated inhibition of tumor angiogenesis by natural killer T-cell ligand, alpha-galactosylceramide. Blood 100:1728–1733

    PubMed  CAS  Google Scholar 

  44. Schmieg, J., G. Yang, R.W. Franck, and M. Tsuji. 2003. Superior protection against malaria and melanoma metastases by a C-glycoside analogue of the natural killer T cell ligand alpha-Galactosylceramide. J Exp Med 198:1631–1641

    Article  PubMed  CAS  Google Scholar 

  45. Kitamura, H., K. Iwakabe, T. Yahata, S. Nishimura, A. Ohta, Y. Ohmi, M. Sato, K. Takeda, K. Okumura, L. Van Kaer, T. Kawano, M. Taniguchi, and T. Nishimura. 1999. The natural killer T (NKT) cell ligand alpha-galactosylceramide demonstrates its immunopotentiating effect by inducing interleukin (IL)-12 production by dendritic cells and IL-12 receptor expression on NKT cells. J Exp Med 189:1121–1128

    Article  PubMed  CAS  Google Scholar 

  46. Smyth, M.J., N.Y. Crowe, and D.I. Godfrey. 2001. NK cells and NKT cells collaborate in host protection from methylcholanthrene-induced fibrosarcoma. Int Immunol 13:459–463

    Article  PubMed  CAS  Google Scholar 

  47. Crowe, N.Y., M.J. Smyth, and D.I. Godfrey. 2002. A critical role for natural killer T cells in immunosurveillance of methylcholanthrene-induced sarcomas. J Exp Med 196:119–127

    Article  PubMed  CAS  Google Scholar 

  48. Nishikawa, H., T. Kato, K. Tanida, A. Hiasa, I. Tawara, H. Ikeda, Y. Ikarashi, H. Wakasugi, M. Kronenberg, T. Nakayama, M. Taniguchi, K. Kuribayashi, L.J. Old, and H. Shiku. 2003. CD4+ CD25+ T cells responding to serologically defined autoantigens suppress antitumor immune responses. Proc Natl Acad Sci U S A 100:10902–10906

    Article  PubMed  CAS  Google Scholar 

  49. Terabe, M., S. Matsui, N. Noben-Trauth, H. Chen, C. Watson, D.D. Donaldson, D.P. Carbone, W.E. Paul, and J.A. Berzofsky. 2000. NKT cell-mediated repression of tumor immunosurveillance by IL-13 and the IL-4R-STAT6 pathway. Nat Immunol 1:515–520

    Article  PubMed  CAS  Google Scholar 

  50. Ostrand-Rosenberg, S., V.K. Clements, M. Terabe, J.M. Park, J.A. Berzofsky, and S.K. Dissanayake. 2002. Resistance to metastatic disease in STAT6-deficient mice requires hemopoietic and nonhemopoietic cells and is IFN-gamma dependent. J Immunol 169:5796–5804

    PubMed  CAS  Google Scholar 

  51. Terabe, M., S. Matsui, J.M. Park, M. Mamura, N. Noben-Trauth, D.D. Donaldson, W. Chen, S.M. Wahl, S. Ledbetter, B. Pratt, J.J. Letterio, W.E. Paul, and J.A. Berzofsky. 2003. Transforming growth factor-beta production and myeloid cells are an effector mechanism through which CD1d-restricted T cells block cytotoxic T lymphocyte-mediated tumor immunosurveillance: abrogation prevents tumor recurrence. J Exp Med 198:1741–1752

    Article  PubMed  CAS  Google Scholar 

  52. Moodycliffe, A.M., D. Nghiem, G. Clydesdale, and S.E. Ullrich. 2000. Immune suppression and skin cancer development: regulation by NKT cells. Nat Immunol 1:521–525

    Article  PubMed  CAS  Google Scholar 

  53. Sharif, S., G.A. Arreaza, P. Zucker, Q.S. Mi, J. Sondhi, O.V. Naidenko, M. Kronenberg, Y. Koezuka, T.L. Delovitch, J.M. Gombert, M. Leite-De-Moraes, C. Gouarin, R. Zhu, A. Hameg, T. Nakayama, M. Taniguchi, F. Lepault, A. Lehuen, J.F. Bach, and A. Herbelin. 2001. Activation of natural killer T cells by alpha-galactosylceramide treatment prevents the onset and recurrence of autoimmune Type 1 diabetes. Nat Med 7:1057–1062

    Article  PubMed  CAS  Google Scholar 

  54. Smyth, M.J., N.Y. Crowe, Y. Hayakawa, K. Takeda, H. Yagita, and D.I. Godfrey. 2002. NKT cells - conductors of tumor immunity? Curr Opin Immunol 14:165–171

    Article  PubMed  CAS  Google Scholar 

  55. Tahir, S.M., O. Cheng, A. Shaulov, Y. Koezuka, G.J. Bubley, S.B. Wilson, S.P. Balk, and M.A. Exley. 2001. Loss of IFN-gamma production by invariant NK T cells in advanced cancer. J Immunol 167:4046–4050

    PubMed  CAS  Google Scholar 

  56. Dhodapkar, M.V., M.D. Geller, D.H. Chang, K. Shimizu, S. Fujii, K.M. Dhodapkar, and J. Krasovsky. 2003. A reversible defect in natural killer T cell function characterizes the progression of premalignant to malignant multiple myeloma. J Exp Med 197:1667–1676

    Article  PubMed  CAS  Google Scholar 

  57. Dhodapkar, K.M., B. Cirignano, F. Chamian, D. Zagzag, D.C. Miller, J.L. Finlay, and R.M. Steinman. 2004. Invariant natural killer T cells are preserved in patients with glioma and exhibit antitumor lytic activity following dendritic cell-mediated expansion. Int J Cancer 109:h893–899.

    Google Scholar 

  58. Metelitsa, L.S., O.V. Naidenko, A. Kant, H.W. Wu, M.J. Loza, B. Perussia, M. Kronenberg, and R.C. Seeger. 2001. Human NKT cells mediate antitumor cytotoxicity directly by recognizing target cell CD1d with bound ligand or indirectly by producing IL-2 to activate NK cells. J Immunol 167:3114–3122

    PubMed  CAS  Google Scholar 

  59. Giaccone, G., C.J. Punt, Y. Ando, R. Ruijter, N. Nishi, M. Peters, B.M. von Blomberg, R.J. Scheper, H.J. van der Vliet, A.J. van den Eertwegh, M. Roelvink, J. Beijnen, H. Zwierzina, and H.M. Pinedo. 2002. A phase I study of the natural killer T-cell ligand alpha-galactosylceramide (KRN7000) in patients with solid tumors. Clin Cancer Res 8:3702–3709

    PubMed  CAS  Google Scholar 

  60. Fujii, S., K. Shimizu, R.M. Steinman, and M.V. Dhodapkar. 2003. Detection and activation of human Valpha24+ natural killer T cells using alpha-galactosyl ceramide-pulsed dendritic cells. J Immunol Methods 272:147–159

    Article  PubMed  CAS  Google Scholar 

  61. van der Vliet, H.J., J.W. Molling, N. Nishi, A.J. Masterson, W. Kolgen, S.A. Porcelli, A.J. van den Eertwegh, B.M. von Blomberg, H.M. Pinedo, G. Giaccone, and R.J. Scheper. 2003. Polarization of Valpha24+ Vbeta11+ natural killer T cells of healthy volunteers and cancer patients using alpha-galactosylceramide-loaded and environmentally instructed dendritic cells. Cancer Res 63:h4101–4106.

    Google Scholar 

  62. Fujii, S., K. Shimizu, M. Kronenberg, and R.M. Steinman. 2002. Prolonged IFN-gamma-producing NKT response induced with alpha-galactosylceramide-loaded DCs. Nat Immunol 3:867–874

    Article  PubMed  CAS  Google Scholar 

  63. Nieda, M., M. Okai, A. Tazbirkova, H. Lin, A. Yamaura, K. Ide, R. Abraham, T. Juji, D.J. Macfarlane, and A.J. Nicol. 2004. Therapeutic activation of Valpha24+Vbeta11+ NKT cells in human subjects results in highly coordinated secondary activation of acquired and innate immunity. Blood 103:383–389

    Article  PubMed  CAS  Google Scholar 

  64. Chang, D.H., K. Osman, J. Connolly, A. Kukreja, J. Krasovsky, M. Pack, A. Hutchinson, M. Geller, N. Liu, R. Annable, J. Shay, K. Kirchhoff, N. Nishi, Y. Ando, K. Hayashi, H. Hassoun, R.M. Steinman, and M.V. Dhodapkar. 2005. Sustained expansion of NKT cells and antigen-specific hT cells after injection of alpha-galactosyl-ceramide loaded mature dendritic cells in cancer patients. J Exp Med 201:1503–1517

    Article  PubMed  CAS  Google Scholar 

  65. Fujii, S.I., K. Shimuzu, M. Kronenberg, and R.M. Steinman. 2002. Prolonged interferon-g producing NKT responses induced with a-galactosyl ceramide loaded dendritic cells. Nature Immunol 3:867–874.

    Article  CAS  Google Scholar 

  66. Steinman, R.M., and M. Dhodapkar. 2001. Active immunization against cancer with dendritic cells: the near future. Int J Cancer 94:459–473

    Article  PubMed  CAS  Google Scholar 

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Dhodapkar, M.V. (2007). The Role of Natural Killer T cells in Tumor Immunity. In: Kaufman, H.L., Wolchok, J.D. (eds) General Principles of Tumor Immunotherapy. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6087-8_4

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