title: Invariant natural killer T cells in hematopoietic stem cell transplantation: killer choice for natural suppression.
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.
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Guan
authors.affiliation: Division of Infectious Diseases, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: H
authors.identifier: http://orcid.org/0000-0001-6532-8478
authors.initials: H
authors.lastname: Bassiri
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: N P
authors.initials: NP
authors.lastname: Patel
authors.affiliation: Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Nichols
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, MI, USA.
authors.forename: R
authors.initials: R
authors.lastname: Das
mesh_terms: D006086:Graft vs Host Disease; D020544:Graft vs Leukemia Effect; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D055611:Natural Killer T-Cells / Q000276:immunology*; D014181:Transplantation Immunology