title: Immunotherapeutic strategies targeting natural killer T cell responses in cancer.
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.
authors.affiliation: 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.
authors.forename: Susannah C
authors.initials: SC
authors.lastname: Shissler
authors.affiliation: 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.
authors.forename: Dominique R
authors.initials: DR
authors.lastname: Bollino
authors.affiliation: 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.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Tiper
authors.affiliation: 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.
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Bates
authors.affiliation: 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.
authors.forename: Roshanak
authors.initials: R
authors.lastname: Derakhshandeh
authors.affiliation: 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. twebb@som.umaryland.edu.
authors.forename: Tonya J
authors.initials: TJ
authors.lastname: Webb
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell
keywords: CD1d; Cancer immunotherapy; NKT cells; α-Galactosylceramide