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Therapeutic Approaches Utilising NKT Cells

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Natural Killer T cells

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Natural killer T (NKT) cells are members of the immune armamentarium with profound immunoregulatory effects. They bridge the innate and adaptive immune systems, filling a niche in recognizing glycolipid antigens, and responding rapidly to prime subsequent immune responses. In cancer, type I NKT cells, defined by their semi-invariant T cell receptor (TCR) using Vα14Jα18 in mice and Vα24Jα18 in humans, are mostly host protective, by producing interferon-γ (IFN-γ) to activate and mature dendritic cells (DC) to make IL-12, which in turn activates NK and CD8+ T cells. In contrast, type II NKT cells, characterized by more diverse TCRs recognizing lipids presented by CD1d, primarily inhibited anti-tumor immunity. This chapter will discuss the impact of CD1d-restricted NKT cells in tumor immune surveillance and immunotherapy and highlight recent therapeutic approaches in tumor mouse models with a focus on harnessing the anti-tumor activities of NKT cells.

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References

  • Ambrosino, E., Berzofsky, J. A. and Terabe, M. (2008). Regulation of tumor immunity: the role of NKT cells. Expert Opin Biol Ther 8(6): 725–34.

    Article  PubMed  CAS  Google Scholar 

  • Ambrosino, E., Terabe, M., Halder, R. C., et al. (2007). Cross-regulation between type I and type II NKT cells in regulating tumor immunity: a new immunoregulatory axis. J Immunol 179(8): 5126–36.

    PubMed  CAS  Google Scholar 

  • Aymeric, L., Apetoh, L., Ghiringhelli, F., et al. (2010). Tumor cell death and ATP release prime dendritic cells and efficient anticancer immunity. Cancer Res 70(3): 855–8.

    Article  PubMed  CAS  Google Scholar 

  • Bagnara, D., Ibatici, A., Corselli, M., et al. (2009). Adoptive immunotherapy mediated by ex vivo expanded natural killer T cells against CD1d-expressing lymphoid neoplasms. Haematologica 94(7): 967–75.

    Article  PubMed  CAS  Google Scholar 

  • Barral, P., Eckl-Dorna, J., Harwood, N. E., et al. (2008). B cell receptor-mediated uptake of CD1d-restricted antigen augments antibody responses by recruiting invariant NKT cell help in vivo. Proc Natl Acad Sci USA 105(24): 8345–50.

    Article  PubMed  CAS  Google Scholar 

  • Bellone, M., Ceccon, M., Grioni, M., et al. (2010). iNKT cells control mouse spontaneous carcinoma independently of tumor-specific cytotoxic T cells. PLoS One 5(1): e8646.

    Article  PubMed  Google Scholar 

  • Berzofsky, J. A. and Terabe, M. (2008). NKT cells in tumor immunity: opposing subsets define a new immunoregulatory axis. J Immunol 180(6): 3627–35.

    PubMed  CAS  Google Scholar 

  • Bezbradica, J. S., Stanic, A. K., Matsuki, N., et al. (2005). Distinct Roles of Dendritic Cells and B Cells in Va14Ja18 Natural T Cell Activation In Vivo. J Immunol 174(8): 4696–705.

    PubMed  CAS  Google Scholar 

  • Burdin, N., Brossay, L. and Kronenberg, M. (1999). Immunization with alpha-galactosylceramide polarizes CD1-reactive NK T cells towards Th2 cytokine synthesis. European Journal of Immunology 29(6): 2014–25.

    Article  PubMed  CAS  Google Scholar 

  • Cabaniols, J. P., Fazilleau, N., Casrouge, A., et al. (2001). Most alpha/beta T cell receptor diversity is due to terminal deoxynucleotidyl transferase. J Exp Med 194(9): 1385–90.

    Article  PubMed  CAS  Google Scholar 

  • Cardell, S., Tangri, S., Chan, S., et al. (1995). CD1-restricted CD4+ T cells in major histocompatibility complex class II-deficient mice. J Exp Med 182(4): 993–1004.

    Article  PubMed  CAS  Google Scholar 

  • Chang, D. H., Osman, K., Connolly, J., et al. (2005). Sustained expansion of NKT cells and antigen-specific T cells after injection of alpha-galactosyl-ceramide loaded mature dendritic cells in cancer patients. J Exp Med 201(9): 1503–17.

    Article  PubMed  CAS  Google Scholar 

  • Chiu, Y. H., Jayawardena, J., Weiss, A., et al. (1999). Distinct subsets of CD1d-restricted T cells recognize self-antigens loaded in different cellular compartments. J Exp Med 189(1): 103–10.

    Article  PubMed  CAS  Google Scholar 

  • Chung, Y., Chang, W. S., Kim, S., et al. (2004). NKT cell ligand alpha-galactosylceramide blocks the induction of oral tolerance by triggering dendritic cell maturation. Eur J Immunol 34(9): 2471–9.

    Article  PubMed  CAS  Google Scholar 

  • Chung, Y., Qin, H., Kang, C. Y., et al. (2007). An NKT-mediated autologous vaccine generates CD4 T cell-dependent potent anti-lymphoma immunity. Blood 110(6): 2013–9.

    Article  PubMed  CAS  Google Scholar 

  • Coquet, J. M., Chakravarti, S., Kyparissoudis, K., et al. (2008). Diverse cytokine production by NKT cell subsets and identification of an IL-17-producing CD4-NK1.1- NKT cell population. Proc Natl Acad Sci USA 105(32): 11287–92.

    Article  PubMed  CAS  Google Scholar 

  • Crowe, N. Y., Coquet, J. M., Berzins, S. P., et al. (2005). Differential antitumor immunity mediated by NKT cell subsets in vivo. J Exp Med 202(9): 1279–88.

    Article  PubMed  CAS  Google Scholar 

  • Crowe, N. Y., Smyth, M. J. and Godfrey, D. I. (2002). A critical role for natural killer T cells in immunosurveillance of methylcholanthrene-induced sarcomas. Journal of Experimental Medicine 196(1): 119–27.

    Article  PubMed  CAS  Google Scholar 

  • Crowe, N. Y., Uldrich, A. P., Kyparissoudis, K., et al. (2003). Glycolipid Antigen Drives Rapid Expansion and Sustained Cytokine Production by NK T Cells. J Immunol 171(8): 4020–27.

    PubMed  CAS  Google Scholar 

  • Demaria, S., Bhardwaj, N., McBride, W. H., et al. (2005). Combining radiotherapy and immunotherapy: a revived partnership. Int J Radiat Oncol Biol Phys 63(3): 655–66.

    Article  PubMed  Google Scholar 

  • Dhodapkar, M. V., Geller, M. D., Chang, D. H., et al. (2003). A reversible defect in natural killer T cell function characterizes the progression of premalignant to malignant multiple myeloma. J Exp Med 197(12): 1667–76.

    Article  PubMed  CAS  Google Scholar 

  • Dunn, G. P., Bruce, A. T., Ikeda, H., et al. (2002). Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 3(11): 991–8.

    Article  PubMed  CAS  Google Scholar 

  • Dunn, G. P., Old, L. J. and Schreiber, R. D. (2004). The three Es of cancer immunoediting. Annu Rev Immunol 22: 329–60.

    Article  PubMed  CAS  Google Scholar 

  • Fujii, S., Shimizu, K., Klimek, V., et al. (2003a). Severe and selective deficiency of interferon-gamma-producing invariant natural killer T cells in patients with myelodysplastic syndromes. Br J Haematol 122(4): 617–22.

    Article  PubMed  Google Scholar 

  • Fujii, S., Shimizu, K., Kronenberg, M., et al. (2002). Prolonged IFN-gamma-producing NKT response induced with alpha-galactosylceramide-loaded DCs. Nature Immunology 3(9): 867–74.

    Article  PubMed  CAS  Google Scholar 

  • Fujii, S., Shimizu, K., Smith, C., et al. (2003b). 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(2): 267–79.

    Article  PubMed  CAS  Google Scholar 

  • Fujii, S., Shimizu, K., Steinman, R. M., et al. (2003c). Detection and activation of human Valpha24+ natural killer T cells using alpha-galactosyl ceramide-pulsed dendritic cells. J Immunol Methods 272(1–2): 147–59.

    Article  PubMed  CAS  Google Scholar 

  • Galli, G., Nuti, S., Tavarini, S., et al. (2003). CD1d-restricted help to B cells by human invariant natural killer T lymphocytes. J Exp Med 197(8): 1051–7.

    Article  PubMed  CAS  Google Scholar 

  • Galli, G., Pittoni, P., Tonti, E., et al. (2007). Invariant NKT cells sustain specific B cell responses and memory. Proc Natl Acad Sci USA 104(10): 3984–9.

    Article  PubMed  CAS  Google Scholar 

  • Godfrey, D. I., MacDonald, H. R., Kronenberg, M., et al. (2004). NKT cells: what’s in a name? Nat Rev Immunol 4(3): 231–7.

    Article  PubMed  CAS  Google Scholar 

  • Godfrey, D. I., Stankovic, S. and Baxter, A. G. (2010). Raising the NKT cell family. Nat Immunol 11(3): 197–206.

    Article  PubMed  CAS  Google Scholar 

  • Harada, M., Seino, K., Wakao, H., et al. (2004). Down-regulation of the invariant Valpha14 antigen receptor in NKT cells upon activation. Int Immunol 16(2): 241–7.

    Article  PubMed  CAS  Google Scholar 

  • Hayakawa, Y., Godfrey, D. I. and Smyth, M. J. (2004). Alpha-galactosylceramide: potential immunomodulatory activity and future application. Curr Med Chem 11(2): 241–52.

    Article  PubMed  CAS  Google Scholar 

  • Hayakawa, Y., Rovero, S., Forni, G., et al. (2003). Alpha-galactosylceramide (KRN7000) suppression of chemical- and oncogene-dependent carcinogenesis. Proc Natl Acad Sci USA 100(16): 9464–9.

    Article  PubMed  CAS  Google Scholar 

  • Hayakawa, Y., Takeda, K., Yagita, H., et al. (2002). IFN-gamma-mediated inhibition of tumor angiogenesis by natural killer T-cell ligand, alpha-galactosylceramide. Blood 100(5): 1728–33.

    PubMed  CAS  Google Scholar 

  • Haynes, N. M., van der Most, R. G., Lake, R. A., et al. (2008). Immunogenic anti-cancer chemotherapy as an emerging concept. Curr Opin Immunol 20(5): 545–57.

    Article  PubMed  CAS  Google Scholar 

  • Hermans, I. F., Silk, J. D., Gileadi, U., et al. (2007). Dendritic Cell Function Can Be Modulated through Cooperative Actions of TLR Ligands and Invariant NKT Cells. J Immunol 178(5): 2721–9.

    PubMed  CAS  Google Scholar 

  • Hermans, I. F., Silk, J. D., Gileadi, U., et al. (2003). NKT cells enhance CD4+ and CD8+ T cell responses to soluble antigen in vivo through direct interaction with dendritic cells. J Immunol 171(10): 5140–7.

    PubMed  CAS  Google Scholar 

  • Hong, C., Lee, H., Park, Y. K., et al. (2009). Regulation of secondary antigen-specific CD8(+) T-cell responses by natural killer T cells. Cancer Res 69(10): 4301–8.

    Article  PubMed  CAS  Google Scholar 

  • Ishikawa, A., Motohashi, S., Ishikawa, E., et al. (2005). A phase I study of alpha-galactosylceramide (KRN7000)-pulsed dendritic cells in patients with advanced and recurrent non-small cell lung cancer. Clin Cancer Res 11(5): 1910–7.

    Article  PubMed  CAS  Google Scholar 

  • Kamijuku, H., Nagata, Y., Jiang, X., et al. (2008). Mechanism of NKT cell activation by intranasal coadministration of alpha-galactosylceramide, which can induce cross-protection against influenza viruses. Mucosal Immunol 1(3): 208–18.

    Article  PubMed  CAS  Google Scholar 

  • Ko, S. Y., Ko, H. J., Chang, W. S., et al. (2005). {alpha}-Galactosylceramide Can Act As a Nasal Vaccine Adjuvant Inducing Protective Immune Responses against Viral Infection and Tumor. J Immunol 175(5): 3309–17.

    PubMed  CAS  Google Scholar 

  • Kunii, N., Horiguchi, S., Motohashi, S., et al. (2009). Combination therapy of in vitro-expanded natural killer T cells and alpha-galactosylceramide-pulsed antigen-presenting cells in patients with recurrent head and neck carcinoma. Cancer Sci 100(6): 1092–8.

    Article  PubMed  CAS  Google Scholar 

  • Lake, R. A. and Robinson, B. W. (2005). Immunotherapy and chemotherapy--a practical partnership. Nat Rev Cancer 5(5): 397–405.

    Article  PubMed  CAS  Google Scholar 

  • Leadbetter, E. A., Brigl, M., Illarionov, P., et al. (2008). NK T cells provide lipid antigen-specific cognate help for B cells. Proc Natl Acad Sci USA 105(24): 8339–44.

    Article  PubMed  CAS  Google Scholar 

  • Lin, H., Nieda, M. and Nicol, A. J. (2004). Differential proliferative response of NKT cell subpopulations to in vitro stimulation in presence of different cytokines. Eur J Immunol 34(10): 2664.

    Article  PubMed  CAS  Google Scholar 

  • Liu, K., Idoyaga, J., Charalambous, A., et al. (2005). Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells. J Exp Med 202(11): 1507–16.

    Article  PubMed  CAS  Google Scholar 

  • Matsuda, J. L., Mallevaey, T., Scott-Browne, J., et al. (2008). CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system. Curr Opin Immunol 20(8): 358–68.

    Article  PubMed  CAS  Google Scholar 

  • Matsui, K., Yoshimoto, T., Tsutsui, H., et al. (1997). Propionibacterium acnes treatment diminishes CD4+ NK1.1+ T cells but induces type I T cells in the liver by induction of IL-12 and IL-18 production from Kupffer cells. J Immunol 159: 97–106.

    Article  PubMed  CAS  Google Scholar 

  • Mattarollo, S. R., Kenna, T., Nieda, M., et al. (2006). Chemotherapy pretreatment sensitizes solid tumor-derived cell lines to Valpha24(+) NKT cell-mediated cytotoxicity. Int J Cancer 119(7): 1630–7.

    Article  PubMed  CAS  Google Scholar 

  • McCarthy, C., Shepherd, D., Fleire, S., et al. (2007). The length of lipids bound to human CD1d molecules modulates the affinity of NKT cell TCR and the threshold of NKT cell activation. J Exp Med 204(5): 1131–44.

    Article  PubMed  CAS  Google Scholar 

  • Miyamoto, K., Miyake, S. and Yamamura, T. (2001). A synthetic glycolipid prevents autoimmune encephalomyelitis by inducing T(H)2 bias of natural killer T cells. Nature 413(6855): 531–34.

    Article  PubMed  CAS  Google Scholar 

  • Molling, J. W., Langius, J. A., Langendijk, J. A., et al. (2007). Low levels of circulating invariant natural killer T cells predict poor clinical outcome in patients with head and neck squamous cell carcinoma. J Clin Oncol 25(7): 862–8.

    Article  PubMed  Google Scholar 

  • Molling, J. W., Moreno, M., de Groot, J., et al. (2008). Chronically stimulated mouse invariant NKT cell lines have a preserved capacity to enhance protection against experimental tumor metastases. Immunol Lett 118(1): 36–43.

    Article  PubMed  CAS  Google Scholar 

  • Moodycliffe, A. M., Nghiem, D., Clydesdale, G., et al. (2000). Immune suppression and skin cancer development: regulation by NKT cells. Nat Immunol 1(6): 521–5.

    Article  PubMed  CAS  Google Scholar 

  • Motohashi, S., Ishikawa, A., Ishikawa, E., et al. (2006). A phase I study of in vitro expanded natural killer T cells in patients with advanced and recurrent non-small cell lung cancer. Clin Cancer Res 12(20 Pt 1): 6079–86.

    Article  PubMed  CAS  Google Scholar 

  • Nakagawa, R., Motoki, K., Nakamura, H., et al. (1998a). Antitumor activity of alpha-­galactosylceramide, KRN7000, in mice with EL-4 hepatic metastasis and its cytokine production. Oncology Research 10(11–12): 561–68.

    PubMed  CAS  Google Scholar 

  • Nakagawa, R., Motoki, K., Ueno, H., et al. (1998b). Treatment of hepatic metastasis of the colon26 adenocarcinoma with an alpha-galactosylceramide, KRN7000. Cancer Res 58(6): 1202–7.

    PubMed  CAS  Google Scholar 

  • Nieda, M., Okai, M., Tazbirkova, A., et al. (2004). Therapeutic activation of V{alpha}24  +  V{beta}11+ NKT cells in human subjects results in highly coordinated secondary activation of acquired and innate immunity. Blood 103(2): 383–89.

    Article  PubMed  CAS  Google Scholar 

  • Nishi, N., van der Vliet, H. J. J., Koezuka, Y., et al. (2000). Synergistic effect of KRN7000 with interleukin-15,-7, and-2 on the expansion of human V alpha 24(+)V beta 11(+) T cells in vitro. Human Immunology 61(4): 357–65.

    Article  PubMed  CAS  Google Scholar 

  • Nishikawa, H., Kato, T., Tanida, K., et al. (2003). CD4+ CD25+ T cells responding to serologically defined autoantigens suppress antitumor immune responses. Proc Natl Acad Sci USA 100(19): 10902–6.

    Article  PubMed  CAS  Google Scholar 

  • Parekh, V. V., Wilson, M. T., Olivares-Villagomez, D., et al. (2005). Glycolipid antigen induces long-term natural killer T cell anergy in mice. J Clin Invest 115(9): 2572–83.

    Article  PubMed  CAS  Google Scholar 

  • Park, J. M., Terabe, M., Donaldson, D. D., et al. (2008). Natural immunosurveillance against spontaneous, autochthonous breast cancers revealed and enhanced by blockade of IL-13-mediated negative regulation. Cancer Immunol Immunother 57(6): 907–12.

    Article  PubMed  CAS  Google Scholar 

  • Park, S. H., Weiss, A., Benlagha, K., et al. (2001). The mouse CD1d-restricted repertoire is dominated by a few autoreactive T cell receptor families. J Exp Med 193(8): 893–904.

    Article  PubMed  CAS  Google Scholar 

  • Petersen, T. R., Sika-Paotonu, D., Knight, D. A., et al. (2010). Potent anti-tumor responses to immunization with dendritic cells loaded with tumor tissue and an NKT cell ligand. Immunol Cell Biol doi:10.1038/icb.2010.9.

  • Renukaradhya, G. J., Khan, M. A., Vieira, M., et al. (2008). Type I NKT cells protect (and Type II NKT cells suppress) the host’s innate antitumor immune response to a B cell lymphoma. Blood 111(12): 5637–45.

    Article  PubMed  CAS  Google Scholar 

  • Schmieg, J., Yang, G., Franck, R. W., et al. (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(11): 1631–41.

    Article  PubMed  CAS  Google Scholar 

  • Schmieg, J., Yang, G., Franck, R. W., et al. (2005). Glycolipid presentation to natural killer T cells differs in an organ-dependent fashion. Proc Natl Acad Sci USA 102(4): 1127–32.

    Article  PubMed  CAS  Google Scholar 

  • Sfondrini, L., Besusso, D., Zoia, M. T., et al. (2002). Absence of the CD1 molecule up-regulates antitumor activity induced by CpG oligodeoxynucleotides in mice. Journal of Immunology 169(1): 151–58.

    CAS  Google Scholar 

  • Shimizu, K., Goto, A., Fukui, M., et al. (2007a). Tumor Cells Loaded with {alpha}-Galactosylceramide Induce Innate NKT and NK Cell-Dependent Resistance to Tumor Implantation in Mice. J Immunol 178(5): 2853–61.

    PubMed  CAS  Google Scholar 

  • Shimizu, K., Kurosawa, Y., Taniguchi, M., et al. (2007b). Cross-presentation of glycolipid from tumor cells loaded with {alpha}-galactosylceramide leads to potent and long-lived T cell mediated immunity via dendritic cells. J Exp Med 204(11): 2641–53.

    Article  PubMed  CAS  Google Scholar 

  • Shin, Y., Hong, C., Lee, H., et al. (2010). NKT Cell-Dependent Regulation of Secondary Antigen-Specific, Conventional CD4+ T Cell Immune Responses. J Immunol doi:10.4049/jimmunol.0903121.

  • Silk, J. D., Hermans, I. F., Gileadi, U., et al. (2004). Utilizing the adjuvant properties of CD1d-dependent NK T cells in T cell-mediated immunotherapy. J Clin Invest 114(12): 1800–11.

    PubMed  CAS  Google Scholar 

  • Silk, J. D., Salio, M., Reddy, B. G., et al. (2008). Cutting edge: nonglycosidic CD1d lipid ligands activate human and murine invariant NKT cells. J Immunol 180(10): 6452–6.

    PubMed  CAS  Google Scholar 

  • Smyth, M. J., Cretney, E., Takeda, K., et al. (2001). Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) contributes to interferon gamma-dependent natural killer cell protection from tumor metastasis. Journal of Experimental Medicine 193(6): 661–70.

    Article  PubMed  CAS  Google Scholar 

  • Smyth, M. J., Crowe, N. Y., Pellicci, D. G., et al. (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(4): 1259–66.

    Article  PubMed  CAS  Google Scholar 

  • Smyth, M. J., Swann, J. and Hayakawa, Y. (2007). Innate tumor immune surveillance. Adv Exp Med Biol 590: 103–11.

    Article  PubMed  Google Scholar 

  • Smyth, M. J., Thia, K. Y. T., Street, S. E. A., et al. (2000). Differential tumor surveillance by natural killer (NK) and NKT cells. Journal of Experimental Medicine 191(4): 661–68.

    Article  PubMed  CAS  Google Scholar 

  • Song, W., van der Vliet, H. J., Tai, Y. T., et al. (2008). Generation of antitumor invariant natural killer T cell lines in multiple myeloma and promotion of their functions via lenalidomide: a strategy for immunotherapy. Clin Cancer Res 14(21): 6955–62.

    Article  PubMed  CAS  Google Scholar 

  • Swann, J. B. and Smyth, M. J. (2007). Immune surveillance of tumors. J Clin Invest 117(5): 1137–46.

    Article  PubMed  CAS  Google Scholar 

  • Swann, J. B., Uldrich, A. P., van Dommelen, S., et al. (2009). Type I NKT cells suppress tumors in mice caused by p53 loss. Blood 113(25): 6382–5.

    Article  PubMed  CAS  Google Scholar 

  • Tachibana, T., Onodera, H., Tsuruyama, T., et al. (2005). Increased Intratumor V{alpha}24-Positive Natural Killer T Cells: A Prognostic Factor for Primary Colorectal Carcinomas. Clin Cancer Res 11(20): 7322–7.

    Article  PubMed  CAS  Google Scholar 

  • Teng, M. W., Sharkey, J., McLaughlin, N. M., et al. (2009a). CD1d-based combination therapy eradicates established tumors in mice. J Immunol 183(3): 1911–20.

    Article  PubMed  CAS  Google Scholar 

  • Teng, M. W., Westwood, J. A., Darcy, P. K., et al. (2007). Combined natural killer T-cell based immunotherapy eradicates established tumors in mice. Cancer Res 67(15): 7495–504.

    Article  PubMed  CAS  Google Scholar 

  • Teng, M. W., Yue, S., Sharkey, J., et al. (2009b). CD1d activation and blockade: a new antitumor strategy. J Immunol 182(6): 3366–71.

    Article  PubMed  CAS  Google Scholar 

  • Terabe, M. and Berzofsky, J. A. (2007). NKT cells in immunoregulation of tumor immunity: a new immunoregulatory axis. Trends Immunol 28: 491–96.

    Article  PubMed  CAS  Google Scholar 

  • Terabe, M., Khanna, C., Bose, S., et al. (2006). CD1d-restricted natural killer T cells can down-regulate tumor immunosurveillance independent of interleukin-4 receptor-signal transducer and activator of transcription 6 or transforming growth factor-beta. Cancer Res 66(7): 3869–75.

    Article  PubMed  CAS  Google Scholar 

  • Terabe, M., Matsui, S., Noben-Trauth, N., et al. (2000). NKT cell-mediated repression of tumor immunosurveillance by IL-13 and the IL-4R-STAT6 pathway. Nature Immunology 1(6): 515–20.

    Article  PubMed  CAS  Google Scholar 

  • Terabe, M., Swann, J., Ambrosino, E., et al. (2005). A nonclassical non-V{alpha}14 J{alpha}18 CD1d-restricted (type II) NKT cell is sufficient for down-regulation of tumor immunosurveillance. J Exp Med 202(12): 1627–33.

    Article  PubMed  CAS  Google Scholar 

  • Toura, I., Kawano, T., Akutsu, Y., et al. (1999). Cutting edge: Inhibition of experimental tumor metastasis by dendritic cells pulsed with alpha-galactosylceramide. Journal of Immunology 163(5): 2387–91.

    CAS  Google Scholar 

  • Uldrich, A. P., Crowe, N. Y., Kyparissoudis, K., et al. (2005). NKT cell stimulation with glycolipid antigen in vivo: costimulation-dependent expansion, bim-dependent contraction, and hyporesponsiveness to further antigenic challenge. J Immunol 175(5): 3092–101.

    PubMed  CAS  Google Scholar 

  • Uno, T., Takeda, K., Kojima, Y., et al. (2006). Eradication of established tumors in mice by a combination antibody-based therapy. Nat Med 12(6): 693–8.

    Article  PubMed  CAS  Google Scholar 

  • van der Most, R. G., Currie, A., Robinson, B. W., et al. (2006). Cranking the immunologic engine with chemotherapy: using context to drive tumor antigen cross-presentation towards useful antitumor immunity. Cancer Res 66(2): 601–4.

    Article  PubMed  Google Scholar 

  • van der Vliet, H. J., Nishi, N., Koezuka, Y., et al. (2001a). Potent expansion of human natural killer T cells using alpha-galactosylceramide (KRN7000)-loaded monocyte-derived dendritic cells, cultured in the presence of IL-7 and IL-15. J Immunol Methods 247(1–2): 61–72.

    Article  PubMed  Google Scholar 

  • van der Vliet, H. J. J., Nishi, N., Koezuka, Y., et al. (2001b). Potent expansion of human natural killer T cells using alpha-galactosylceramide (KRN7000)-loaded monocyte-derived dendritic cells, cultured in the presence of IL-7 and IL-15. Journal of Immunological Methods 247(1–2): 61–72.

    Article  PubMed  Google Scholar 

  • Vonderheide, R. H., Dutcher, J. P., Anderson, J. E., et al. (2001). Phase I study of recombinant human CD40 ligand in cancer patients. J Clin Oncol 19(13): 3280–7.

    PubMed  CAS  Google Scholar 

  • Vonderheide, R. H., Flaherty, K. T., Khalil, M., et al. (2007). Clinical activity and immune modulation in cancer patients treated with CP-870,893, a novel CD40 agonist monoclonal antibody. J Clin Oncol 25(7): 876–83.

    Article  PubMed  CAS  Google Scholar 

  • Wilson, M. T., Johansson, C., Olivares-Villagomez, D., et al. (2003). The response of natural killer T cells to glycolipid antigens is characterized by surface receptor down-modulation and expansion. Proc Natl Acad Sci USA 100(19): 10913–8.

    Article  PubMed  CAS  Google Scholar 

  • Yu, K. O., Im, J. S., Molano, A., et al. (2005). Modulation of CD1d-restricted NKT cell responses by using N-acyl variants of {alpha}-galactosylceramides. Proc Natl Acad Sci USA 102(9): 3383–8.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

SRM was supported by a Balzan Foundation Post-doctoral Fellowship. MJS was supported by a National Health and Medical Research Council of Australia (NH&MRC) Australia Fellowship.

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Authors and Affiliations

  1. Cancer Immunology Program, Peter MacCallum Cancer Centre, Victoria, Australia

    Stephen R. Mattarollo

  2. Immunology, and Metabolic Medicine, The University of Queensland Diamantina Institute for Cancer, Woolloongabba, QLD, Australia

    Stephen R. Mattarollo

  3. Cancer Immunology Program, Peter MacCallum Cancer Centre, 1, A’Beckett St, 8006, Victoria, Australia

    Mark J. Smyth

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  1. Stephen R. Mattarollo
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  2. Mark J. Smyth
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Correspondence to Mark J. Smyth .

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Editors and Affiliations

  1. National Cancer Institute (NCI), Molecular Immunogenetics & Vaccine, National Institutes of Health (NIH), Center Drive 10, Bethesda, 20892-1578, Maryland, USA

    Masaki Terabe

  2. National Cancer Institute, Lab. Developmental &, National Institutes of Health (NIH), Bethesda, 20892, Maryland, USA

    Jay A. Berzofsky

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© 2012 Springer Science+Business Media, LLC

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Mattarollo, S.R., Smyth, M.J. (2012). Therapeutic Approaches Utilising NKT Cells. In: Terabe, M., Berzofsky, J. (eds) Natural Killer T cells. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0613-6_7

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