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DC-Based Immunotherapy Targeting NKT Cells

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Natural Killer T cells

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

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Abstract

A primary focus of tumor immunotherapy research is to modify the immune system so that it becomes immunized and not tolerized to the presentation of antigens by or from tumor cells. Dendritic cells (DCs) are the logical target for the development of tumor immunotherapies, because the DCs instruct the ensuing immune response. For invariant iNKT cell targeted therapy, the glycolipid NKT cell ligand, α-galactosylceramide is loaded on DCs. This treatment resulted in increased numbers of IFN-γ producing cells, and this correlated with antitumor effects. On the other hand, activated iNKT cells demonstrate an adjuvant effect by inducing the maturation of endogenous DCs, thereby linking innate and adaptive immunity. Cross-presentation to T cells is key to this linkage and depends on the CD8a+DC subset and the expression of CD40, CD70, and CCL17 molecules on DCs. Based on these adjuvant mechanisms, we will introduce here new concepts about iNKT cell-targeted adjuvant therapies.

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Acknowledgments

The authors are grateful to Dr. Peter Burrows for peer-reviewing and helpful comments in the preparation of the manuscript. This work is supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to K. Shimizu and S. Fujii) and by a grant of coordination, support and training program for translational research of Japan (to K. Shimizu and S. Fujii).

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Authors and Affiliations

  1. Research Unit for Cellular Immunotherapy, The Institute of Physical and Chemical Research (RIKEN), Research Center for Allergy and Immunology (RCAI), 1-7-22, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan

    Shin-ichiro Fujii

  2. Research Unit for Cellular Immunotherapy, The Institute of Physical and Chemical Research (RIKEN), Research Center for Allergy and Immunology (RCAI), 1-7-22, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, Japan

    Kanako Shimizu

  3. Research Unit for Therapeutic Model, The Institute of Physical and Chemical Research (RIKEN), Research Center for Allergy and Immunology (RCAI), 1-7-22, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, Japan

    Kanako Shimizu

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  1. Shin-ichiro Fujii
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  2. Kanako Shimizu
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Correspondence to Shin-ichiro Fujii .

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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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Fujii, Si., Shimizu, K. (2012). DC-Based Immunotherapy Targeting 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_6

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