How do the different types of natural killer T cells affect immunotherapeutic targeting in pediatric oncology?

Updated: Mar 20, 2018
  • Author: Crystal L Mackall, MD; Chief Editor: Jennifer Reikes Willert, MD  more...
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Natural killer T cells represent another class of cells in which a dichotomy is observed; some subpopulations induce immune activation and antitumor effects, whereas very similar but distinct populations can actually contribute to tumor growth and progression. [33]

For instance, type I (classic) natural killer T cells express the semi-invariant T-cell receptor (TCR) using a unique TCR Vα14Jα18 chain in the mouse and a Vα24Jα18 chain in the human. This TCR recognizes the glycolipid α-galactosylceramide (αGalCer) in association with a nonclassical major histocompatibility complex (MHC) class I molecule called CD1d.

Type I natural killer T cells have been shown to protect against methylcholanthrene-induced sarcomas in vivo, and this effect depends on αGalCer and interleukin (IL)-12 production by dendritic cells (DCs). [34, 35, 36] These cells appear to produce interferon gamma, a cytokine that then recruits natural killer cell and CD8+ T cells to the tumor, leading to lysis.

Type II (nonclassic) natural killer T cells also bind CD1d but lack the Vα24Jα18 chain, have many different TCRs, and, with rare exception, do not recognize αGalCer. This subset is poorly understood but is generally thought to be suppressive of tumor immunosurveillance.

Because of the success of natural killer T cells in eliminating tumors in preclinical mouse models, clinical trials were performed using αGalCer-pulsed DCs and natural killer T cells in patients with lung cancer. Neither administration of the DCs nor adoptive transfer of autologous natural killer T cells activated with αGalCer and IL-2 yielded responses but were well tolerated in phase I trials. [37, 38]

Humans generally have a lower frequency of natural killer T cells, but biologic differences between natural killer T cells in mice and those in humans may explain the disparity; further trials are needed.

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