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A novel immunoregulatory axis of NKT cell subsets regulating tumor immunity

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Abstract

There are many mechanisms that regulate and dampen the immune response to cancers, including several types of regulatory T cells. Besides the T reg cell, we have identified another immunoregulatory circuit initiated by NKT cells that produce IL-13 in response to tumor growth and this IL-13 then induces myeloid cells to make TGF-β that inhibits cytotoxic T cell-mediated tumor immunosurveillance in several mouse tumor models. This finding created a paradox in the role of NKT cells in tumor immunity, in that they can also contribute to protection. We resolve this paradox by the finding that the suppressive NKT cell is a type II NKT cell that lacks the canonical invariant T cell receptor, whereas the protective cell is a type I NKT cell that expresses the invariant receptor. Further, we see that these two subsets of NKT cells counter-regulate each other, defining a new immunoregulatory axis. The balance along this axis may determine the outcome of tumor immunosurveillance as well as influence the efficacy of anti-cancer vaccines and immunotherapy.

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Acknowledgments

We thank our collaborators Elena Ambrosino, Mark Smyth, Jeremy Swann, Yoshihiro Hayakawa, Dale Godfrey, Suzanne Ostrand-Rosenberg, Pratima Sinha, Shun Takaku, Judy Peng, Takashi Yamamura, Sachiko Miyake, Vipin Kumar, and Ramesh Halder for their most valuable collaboration, without which the work reviewed here would not have been possible.

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Correspondence to Jay A. Berzofsky or Masaki Terabe.

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This article is a symposium paper from the conference “Progress in Vaccination against Cancer 2007 (PIVAC 7)”, held in Stockholm, Sweden, on 10–11 September 2007.

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Berzofsky, J.A., Terabe, M. A novel immunoregulatory axis of NKT cell subsets regulating tumor immunity. Cancer Immunol Immunother 57, 1679–1683 (2008). https://doi.org/10.1007/s00262-008-0495-4

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  • DOI: https://doi.org/10.1007/s00262-008-0495-4

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