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Invariant natural killer T cells in hematopoietic stem cell transplantation: killer choice for natural suppression

Bone Marrow Transplantation volume 51, pages 629–637 (2016)Cite this article

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Abstract

Invariant natural killer T cells (iNKTs) are innate-like lipid-reactive T lymphocytes that express an invariant T-cell receptor (TCR). Following engagement of the iTCR, iNKTs rapidly secrete copious amounts of Th1 and Th2 cytokines and promote the functions of several immune cells including NK, T, B and dendritic cells. Accordingly, iNKTs bridge the innate and adaptive immune responses and modulate susceptibility to autoimmunity, infection, allergy and cancer. Allogeneic hematopoietic stem cell transplantation (HSCT) is one of the most effective treatments for patients with hematologic malignancies. However, the beneficial graft versus leukemia (GvL) effect mediated by the conventional T cells contained within the allograft is often hampered by the concurrent occurrence of graft versus host disease (GvHD). Thus, developing strategies that can dissociate GvHD from GvL remain clinically challenging. Several preclinical and clinical studies demonstrate that iNKTs significantly attenuate GvHD without abrogating the GvL effect. Besides preserving the GvL activity of the donor graft, iNKTs themselves exert antitumor immune responses via direct and indirect mechanisms. Herein, we review the various mechanisms by which iNKTs provide antitumor immunity and discuss their roles in GvHD suppression. We also highlight the opportunities and obstacles in manipulating iNKTs for use in the cellular therapy of hematologic malignancies.

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Acknowledgements

This work was supported by grants from Alex’s Lemonade Stand Foundation, SAS Foundation for Cancer Research and Foerderer Award (RD), and Clinical Immunology Society & Talecris Biotherapeutics (HB) and the National Institutes of Health (RD, HB, KEN). We thank Dr Hariharan Subramanian for critically reviewing the manuscript.

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Authors and Affiliations

  1. Division of Oncology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA,

    P Guan & N P Patel

  2. Division of Infectious Diseases, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    H Bassiri

  3. Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA

    K E Nichols

  4. Department of Physiology, Michigan State University, East Lansing, MI, USA

    R Das

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  1. P Guan
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  2. H Bassiri
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  3. N P Patel
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  4. K E Nichols
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Correspondence to R Das.

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Guan, P., Bassiri, H., Patel, N. et al. Invariant natural killer T cells in hematopoietic stem cell transplantation: killer choice for natural suppression. Bone Marrow Transplant 51, 629–637 (2016). https://doi.org/10.1038/bmt.2015.335

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  • DOI: https://doi.org/10.1038/bmt.2015.335

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