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Immunotherapeutic strategies targeting natural killer T cell responses in cancer

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Abstract

Natural killer T (NKT) cells are a unique subset of lymphocytes that bridge the innate and adaptive immune system. NKT cells possess a classic αβ T cell receptor (TCR) that is able to recognize self and foreign glycolipid antigens presented by the nonclassical class I major histocompatibility complex (MHC) molecule, CD1d. Type I NKT cells (referred to as invariant NKT cells) express a semi-invariant Vα14Jα18 TCR in mice and Vα24Jα18 TCR in humans. Type II NKT cells are CD1d-restricted T cells that express a more diverse set of TCR α chains. The two types of NKT cells often exert opposing effects especially in tumor immunity, where type II cells generally suppress tumor immunity while type I NKT cells can enhance anti-tumor immune responses. In this review, we focus on the role of NKT cells in cancer. We discuss their effector and suppressive functions, as well as describe preclinical and clinical studies utilizing therapeutic strategies focused on harnessing their potent anti-tumor effector functions, and conclude with a discussion on potential next steps for the utilization of NKT cell-targeted therapies for the treatment of cancer.

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Acknowledgments

Given the wide breadth of studies examining the role of NKT cells in cancer, only recent reviews and closely related articles have been cited and we apologize to those whose work may have been omitted due to space considerations. The authors have no competing financial interest. This work was supported by grants from the NIH/NCI to TJW.

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  1. Department of Microbiology and Immunology, University of Maryland School of Medicine and the Marlene and Stewart Greenebaum Cancer Center, 685 West Baltimore St; HSF I—Room 380, Baltimore, MD, 21201, USA

    Susannah C. Shissler, Dominique R. Bollino, Irina V. Tiper, Joshua P. Bates, Roshanak Derakhshandeh & Tonya J. Webb

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  1. Susannah C. Shissler
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  2. Dominique R. Bollino
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  3. Irina V. Tiper
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  4. Joshua P. Bates
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  6. Tonya J. Webb
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Correspondence to Tonya J. Webb.

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This article is published in the Special Issue CD1, MR1, NKT, and MAIT: Evolution and Origins of Non-peptidic Antigen Recognition by T lymphocytes with Guest Editor Dr. Dirk Zajonc

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Shissler, S.C., Bollino, D.R., Tiper, I.V. et al. Immunotherapeutic strategies targeting natural killer T cell responses in cancer. Immunogenetics 68, 623–638 (2016). https://doi.org/10.1007/s00251-016-0928-8

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