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Front. Immunol. | doi: 10.3389/fimmu.2018.00367

The role of NKT cells in cancer – a phenotypical and functional approach

 Daniëlle Krijgsman1, Marianne Hokland2 and Peter J. Kuppen1*
  • 1Surgery, Leiden University Medical Center, Netherlands
  • 2Department of Biomedicine, Faculty of Health, Aarhus University, Denmark

Natural killer T (NKT) cells are a subset of CD1d-restricted T cells at the interface between the innate and adaptive immune system. NKT cells can be subdivided into functional subsets that respond rapidly to a wide variety of glycolipids and stress-related proteins using T- or NK cell-like effector mechanisms. Because of their major modulating effects on immune responses via secretion of cytokines, NKT cells are also considered important players in tumor immunosurveillance. During early tumor development, T helper (TH)1-like NKT cell subsets have the potential to rapidly stimulate tumor-specific T cells and effector NK cells that can eliminate tumor cells. In case of tumor progression, NKT cells may become overstimulated and anergic leading to deletion of a part of the NKT cell population in patients via activation-induced cell death. Additionally, the remaining NKT cells become hyporesponsive, or switch to immunosuppressive TH2-/Treg-like NKT cell subsets, thereby facilitating tumor progression and immune escape. In this review, we discuss this important role of NKT cells in tumor development and we conclude that there should be three important focuses of future research in cancer patients in relation with NKT cells: (1) expansion of the NKT cell population, (2) prevention and breaking of NKT cell anergy, and (3) skewing of NKT cells towards TH1-like subsets with anti-tumor activity.

Keywords: Natural Killer T-Cells, tumor immunology, immune escape, Immunotherapy, Cancer

Received: 08 Nov 2017; Accepted: 09 Feb 2018.

Edited by:

JIn S. Im, University of Texas MD Anderson Cancer Center, United States

Reviewed by:

Giulia Casorati, San Raffaele Hospital (IRCCS), Italy
Luc Van Kaer, Vanderbilt University, United States  

Copyright: © 2018 Krijgsman, Hokland and Kuppen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Peter J. Kuppen, Leiden University Medical Center, Surgery, Leiden, Netherlands,