Targeting natural killer cells and natural killer T cells in cancer

Natural killer (NK) cells and natural killer T (NKT) cells are subsets of lymphocytes that share some phenotypical and functional similarities. Both cell types can rapidly respond to the presence of tumour cells and participate in antitumour immune responses. This has prompted interest in the development of innovative cancer therapies that are based on the manipulation of NK and NKT cells. Recent studies have highlighted how the immune reactivity of NK and NKT cells is shaped by the environment in which they develop. The rational use of these cells in cancer immunotherapies awaits a better understanding of their effector functions, migratory patterns and survival properties in humans.

[1]  H. Ljunggren,et al.  In search of the 'missing self': MHC molecules and NK cell recognition. , 1990, Immunology today.

[2]  Baptiste N. Jaeger,et al.  Confinement of Activating Receptors at the Plasma Membrane Controls Natural Killer Cell Tolerance , 2011, Science Signaling.

[3]  P. Rohrlich,et al.  Peripheral T-cell expansion and low infection rate after reduced-intensity conditioning and allogeneic blood stem cell transplantation , 2005, Bone Marrow Transplantation.

[4]  T. Juji,et al.  Therapeutic activation of Valpha24+Vbeta11+ NKT cells in human subjects results in highly coordinated secondary activation of acquired and innate immunity. , 2004, Blood.

[5]  A. Makrigiannis,et al.  Evolution of the Ly49 and Nkrp1 recognition systems. , 2008, Seminars in immunology.

[6]  J. Blay,et al.  Natural killer cell IFN-gamma levels predict long-term survival with imatinib mesylate therapy in gastrointestinal stromal tumor-bearing patients. , 2009, Cancer research.

[7]  H. Spits,et al.  The expanding family of innate lymphoid cells: regulators and effectors of immunity and tissue remodeling , 2011, Nature Immunology.

[8]  T. D. de Gruijl,et al.  Clinical experience with α-galactosylceramide (KRN7000) in patients with advanced cancer and chronic hepatitis B/C infection. , 2011, Clinical immunology.

[9]  M. Koch,et al.  Natural Killer Cells are Scarce in Colorectal Carcinoma Tissue Despite High Levels of Chemokines and Cytokines , 2011, Clinical Cancer Research.

[10]  M. Smyth,et al.  A Critical Role for Natural Killer T Cells in Immunosurveillance of Methylcholanthrene-induced Sarcomas , 2002, The Journal of experimental medicine.

[11]  J. Trapani,et al.  Differential Tumor Surveillance by Natural Killer (Nk) and Nkt Cells , 2000, The Journal of experimental medicine.

[12]  R. Nuscher,et al.  Bone marrow transplantation. , 1977, The American journal of nursing.

[13]  P. Mahadevan,et al.  An overview , 2007, Journal of Biosciences.

[14]  N. Nagarajan,et al.  Cutting Edge: The Mechanism of Invariant NKT Cell Responses to Viral Danger Signals1 , 2008, The Journal of Immunology.

[15]  G. Collins The next generation. , 2006, Scientific American.

[16]  W. Lehmacher,et al.  Increased serum levels of tumor necrosis factor alpha precede major complications of bone marrow transplantation. , 1990, Blood.

[17]  D. Cornfield,et al.  The unexpected effect of cyclosporin A on CD56+CD16- and CD56+CD16+ natural killer cell subpopulations. , 2007, Blood.

[18]  Jelena S. Bezbradica,et al.  Another View of T Cell Antigen Recognition: Cooperative Engagement of Glycolipid Antigens by Va14Ja18 Natural TCR 1 , 2003, The Journal of Immunology.

[19]  T. Blankenstein,et al.  B‐cells and IL‐4 promote methylcholanthrene‐induced carcinogenesis but there is no evidence for a role of T/NKT‐cells and their effector molecules (Fas‐ligand, TNF‐α, perforin) , 2012, International journal of cancer.

[20]  R. Medzhitov,et al.  Intrinsic sensor of oncogenic transformation induces a signal for innate immunosurveillance , 2008, Proceedings of the National Academy of Sciences.

[21]  J. Orange,et al.  Natural killer cells in human health and disease. , 2006, Clinical immunology.

[22]  Kazuyoshi Takeda,et al.  New aspects of natural-killer-cell surveillance and therapy of cancer , 2002, Nature Reviews Cancer.

[23]  A. Gratwohl,et al.  Purified donor NK-lymphocyte infusion to consolidate engraftment after haploidentical stem cell transplantation , 2004, Leukemia.

[24]  M. Tsuji,et al.  Superior Protection against Malaria and Melanoma Metastases by a C-glycoside Analogue of the Natural Killer T Cell Ligand α-Galactosylceramide , 2003, The Journal of experimental medicine.

[25]  Albert Bendelac,et al.  The biology of NKT cells. , 2007, Annual review of immunology.

[26]  Y. Koezuka,et al.  Cutting edge: Cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells. , 1999, Journal of immunology.

[27]  P. Validire,et al.  Profound coordinated alterations of intratumoral NK cell phenotype and function in lung carcinoma. , 2011, Cancer research.

[28]  Eric J. Brown,et al.  The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor , 2005, Nature.

[29]  D. Fremont,et al.  Ligands for murine NKG2D display heterogeneous binding behavior. , 2002, European journal of immunology.

[30]  K. Weinberg,et al.  Expression of CD1d by myelomonocytic leukemias provides a target for cytotoxic NKT cells , 2003, Leukemia.

[31]  L. Boon,et al.  Recipient lymphocyte infusion in MHC-matched bone marrow chimeras induces a limited lymphohematopoietic host-versus-graft reactivity but a significant antileukemic effect mediated by CD8+ T cells and natural killer cells , 2011, Haematologica.

[32]  Michael B Brenner,et al.  CD1: antigen presentation and T cell function. , 2004, Annual review of immunology.

[33]  M. Baccarani,et al.  Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patients. , 2011, Blood.

[34]  T. Tashiro,et al.  Mechanism of NKT cell activation by intranasal coadministration of α-galactosylceramide, which can induce cross-protection against influenza viruses , 2008, Mucosal Immunology.

[35]  J. Berzofsky,et al.  A nonclassical non-Vα14Jα18 CD1d-restricted (type II) NKT cell is sufficient for down-regulation of tumor immunosurveillance , 2005, The Journal of experimental medicine.

[36]  A. Mori,et al.  Increased Intratumor Vα24-Positive Natural Killer T Cells: A Prognostic Factor for Primary Colorectal Carcinomas , 2005, Clinical Cancer Research.

[37]  G. Besra,et al.  B cell receptor-mediated uptake of CD1d-restricted antigen augments antibody responses by recruiting invariant NKT cell help in vivo , 2008, Proceedings of the National Academy of Sciences.

[38]  T. Juji,et al.  Therapeutic activation of Vα24^+Vβ11^+ NKT cells in human subjects results in highly coordinated secondary activation of acquired and innate immunity , 2004 .

[39]  M. Kronenberg,et al.  Homeostasis of V alpha 14i NKT cells. , 2002, Nature immunology.

[40]  L. Moretta,et al.  Identification of PVR (CD155) and Nectin-2 (CD112) as Cell Surface Ligands for the Human DNAM-1 (CD226) Activating Molecule , 2003, The Journal of experimental medicine.

[41]  R. Herberman,et al.  Evaluation of cell-mediated cytotoxic reactivity against tumor associated antigens with 125I-iododeoxyuridine labeled target cells. , 1973, Journal of immunology.

[42]  M. Kronenberg,et al.  Tracking the Response of Natural Killer T Cells to a Glycolipid Antigen Using Cd1d Tetramers , 2000, The Journal of experimental medicine.

[43]  M. Kronenberg,et al.  Homeostasis of Vα14i NKT cells , 2002, Nature Immunology.

[44]  L. Downs,et al.  A phase II study of allogeneic natural killer cell therapy to treat patients with recurrent ovarian and breast cancer. , 2011, Cytotherapy.

[45]  S. Giralt Harnessing Graft-Versus-Leukemia Without Myeloablative Therapy , 2000 .

[46]  Y. Okamoto,et al.  A Phase I Study of In vitro Expanded Natural Killer T Cells in Patients with Advanced and Recurrent Non–Small Cell Lung Cancer , 2006, Clinical Cancer Research.

[47]  Anneliese O. Speak,et al.  Activation of invariant NKT cells by toll-like receptor 9-stimulated dendritic cells requires type I interferon and charged glycosphingolipids. , 2007, Immunity.

[48]  R. Proia,et al.  Lysosomal Glycosphingolipid Recognition by NKT Cells , 2004, Science.

[49]  J. Bell,et al.  HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C , 1998, Nature.

[50]  N. Lee,et al.  Non-CD34+ cells, especially CD8+ cytotoxic T cells and CD56+ natural killer cells, rather than CD34 cells, predict early engraftment and better transplantation outcomes in patients with hematologic malignancies after allogeneic peripheral stem cell transplantation. , 2006, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[51]  H. Macdonald,et al.  Cutting Edge: Influence of the TCR Vβ Domain on the Avidity of CD1d:α-Galactosylceramide Binding by Invariant Vα14 NKT Cells1 , 2003, The Journal of Immunology.

[52]  W. Lehmacher,et al.  Increased serum levels of tumor necrosis factor alpha precede major complications of bone marrow transplantation. , 1990, Blood.

[53]  M. Roizen,et al.  Hallmarks of Cancer: The Next Generation , 2012 .

[54]  Y. Tanaka,et al.  Natural killer-like nonspecific tumor cell lysis mediated by specific ligand-activated Valpha14 NKT cells. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[55]  Eric Vivier,et al.  The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans , 2009, The Journal of experimental medicine.

[56]  A Ferrant,et al.  Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. , 1995, Blood.

[57]  L. Hennighausen,et al.  Genetic evidence supporting selection of the Valpha14i NKT cell lineage from double-positive thymocyte precursors. , 2005, Immunity.

[58]  Lewis L. Lanier,et al.  NK cell development, homeostasis and function: parallels with CD8+ T cells , 2011, Nature Reviews Immunology.

[59]  G. Dranoff,et al.  Cancer immunology—analysis of host and tumor factors for personalized medicine , 2011, Nature Reviews Clinical Oncology.

[60]  E. Kimby,et al.  Safety analysis of ex vivo-expanded NK and NK-like T cells administered to cancer patients: a phase I clinical study. , 2009, Immunotherapy.

[61]  G. Gastl,et al.  Impact of natural killer cell dose and donor killer‐cell immunoglobulin‐like receptor (KIR) genotype on outcome following human leucocyte antigen‐identical haematopoietic stem cell transplantation , 2007, Clinical and experimental immunology.

[62]  W. Linehan,et al.  Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. , 2000, The New England journal of medicine.

[63]  Joseph C. Sun,et al.  Adaptive Immune Features of Natural Killer Cells , 2009, Nature.

[64]  L. Moretta,et al.  Existence of both inhibitory (p58) and activatory (p50) receptors for HLA-C molecules in human natural killer cells , 1995, The Journal of experimental medicine.

[65]  K. Garcia,et al.  The V alpha 14 NKT cell TCR exhibits high-affinity binding to a glycolipid/CD1d complex. , 2002, Journal of immunology.

[66]  Rachel L. Mistur,et al.  Graft-Versus-Host Disease , 2016 .

[67]  L. Moretta,et al.  p46, a Novel Natural Killer Cell–specific Surface Molecule That Mediates Cell Activation , 1997, The Journal of experimental medicine.

[68]  M. Smyth,et al.  CD1d Activation and Blockade: A New Antitumor Strategy1 , 2009, The Journal of Immunology.

[69]  P. Parham,et al.  Donor-recipient combinations of group A and B KIR haplotypes and HLA class I ligand affect the outcome of HLA-matched, sibling donor hematopoietic cell transplantation. , 2007, Human immunology.

[70]  G. Salles,et al.  Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. , 2002, Blood.

[71]  Anneliese O. Speak,et al.  Diverse Endogenous Antigens for Mouse NKT Cells: Self-Antigens That Are Not Glycosphingolipids , 2011, The Journal of Immunology.

[72]  M. Smyth,et al.  Type I natural killer T cells suppress tumors caused by p53 loss in mice. , 2009, Blood.

[73]  H. Ljunggren,et al.  Recognition of beta 2-microglobulin-negative (beta 2m-) T-cell blasts by natural killer cells from normal but not from beta 2m- mice: nonresponsiveness controlled by beta 2m- bone marrow in chimeric mice. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[74]  R. Armitage,et al.  ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor. , 2001, Immunity.

[75]  C. Janeway,et al.  Innate immune recognition. , 2002, Annual review of immunology.

[76]  E. Alici IPH-2101, a fully human anti-NK-cell inhibitory receptor mAb for the potential treatment of hematological cancers. , 2010, Current opinion in molecular therapeutics.

[77]  S. Asgharzadeh,et al.  Valpha24-invariant NKT cells mediate antitumor activity via killing of tumor-associated macrophages. , 2009, The Journal of clinical investigation.

[78]  C. Carnaud,et al.  The Contribution of NKT Cells, NK Cells, and Other γ-Chain-Dependent Non-T Non-B Cells to IL-12-Mediated Rejection of Tumors 1 , 2003, The Journal of Immunology.

[79]  O. Lantz,et al.  The transcription factor PLZF directs the effector program of the NKT cell lineage. , 2008, Immunity.

[80]  J. Bender,et al.  Phase I Trial , 1983 .

[81]  É. Vivier,et al.  Genetic and antibody-mediated reprogramming of natural killer cell missing-self recognition in vivo , 2009, Proceedings of the National Academy of Sciences.

[82]  Franco Locatelli,et al.  Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors. , 2003, Blood.

[83]  L. Teyton,et al.  A Thymic Precursor to the NK T Cell Lineage , 2002, Science.

[84]  M. Kronenberg,et al.  NKT cells derive from double-positive thymocytes that are positively selected by CD1d , 2001, Nature Immunology.

[85]  G. Besra,et al.  Invariant natural killer T cells recognize lipid self-antigen induced by microbial danger signals , 2011, Nature Immunology.

[86]  L. Brossay,et al.  NK Cell–Like Behavior of Vα14i NK T Cells during MCMV Infection , 2008, PLoS pathogens.

[87]  N. Kröger,et al.  Comparison between antithymocyte globulin and alemtuzumab and the possible impact of KIR‐ligand mismatch after dose‐reduced conditioning and unrelated stem cell transplantation in patients with multiple myeloma , 2005, British journal of haematology.

[88]  M. Kronenberg,et al.  Cutting edge: IFN-gamma signaling to macrophages is required for optimal Valpha14i NK T/NK cell cross-talk. , 2005, Journal of immunology.

[89]  P. Savage,et al.  The paradox of immune molecular recognition of alpha-galactosylceramide: low affinity, low specificity for CD1d, high affinity for alpha beta TCRs. , 2003, Journal of immunology.

[90]  D. Campana,et al.  Expansion and activation of natural killer cells for cancer immunotherapy. , 2009, The Korean journal of laboratory medicine.

[91]  E. Ciccone,et al.  Allorecognition by NK cells: nonself or no self? , 1992, Immunology today.

[92]  H. Majima [Phase I clinical study]. , 1984, Gan to kagaku ryoho. Cancer & chemotherapy.

[93]  James M. Wilson,et al.  Natural Killer T Cell Ligand α-Galactosylceramide Enhances Protective Immunity Induced by Malaria Vaccines , 2002, The Journal of experimental medicine.

[94]  J. Schold,et al.  The relationship between circulating natural killer cells after reduced intensity conditioning hematopoietic stem cell transplantation and relapse-free survival and graft-versus-host disease , 2008, Haematologica.

[95]  A. Harris,et al.  NKT Cells Enhance CD4+ and CD8+ T Cell Responses to Soluble Antigen In Vivo through Direct Interaction with Dendritic Cells 1 , 2003, The Journal of Immunology.

[96]  G. Besra,et al.  Modulation of CD1d-restricted NKT cell responses by using N-acyl variants of alpha-galactosylceramides. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[97]  T. Yamamura,et al.  Preferential T(h)2 polarization by OCH is supported by incompetent NKT cell induction of CD40L and following production of inflammatory cytokines by bystander cells in vivo. , 2005, International immunology.

[98]  Liping Yang,et al.  Cytokine-induced memory-like natural killer cells , 2009, Proceedings of the National Academy of Sciences.

[99]  M. Smyth,et al.  CD1-restricted T cells and tumor immunity. , 2007, Current topics in microbiology and immunology.

[100]  Eric O Long,et al.  Recruitment of tyrosine phosphatase HCP by the killer cell inhibitor receptor. , 1996, Immunity.

[101]  M. Sanda,et al.  Defective NKT Cell Activation by CD1d+ TRAMP Prostate Tumor Cells Is Corrected by Interleukin-12 with alpha-Galactosylceramide , 2010, PloS one.

[102]  G. Besra,et al.  Recognition of β-linked self glycolipids mediated by natural killer T cell antigen receptors , 2011, Nature Immunology.

[103]  D. Raulet,et al.  Mature natural killer cells reset their responsiveness when exposed to an altered MHC environment , 2010, The Journal of experimental medicine.

[104]  Peter Parham,et al.  KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. , 2002, Annual review of immunology.

[105]  M. Caligiuri,et al.  IPH2101, a novel anti-inhibitory KIR antibody, and lenalidomide combine to enhance the natural killer cell versus multiple myeloma effect. , 2011, Blood.

[106]  R. Rappuoli,et al.  Invariant NKT cells sustain specific B cell responses and memory , 2007, Proceedings of the National Academy of Sciences.

[107]  R. Vance,et al.  Self-tolerance of natural killer cells , 2006, Nature Reviews Immunology.

[108]  K. Nakachi,et al.  Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population , 2000, The Lancet.

[109]  Laura S. Jacobus,et al.  Rituximab infusion induces NK activation in lymphoma patients with the high-affinity CD16 polymorphism. , 2011, Blood.

[110]  C. Baird,et al.  The pilot study. , 2000, Orthopedic nursing.

[111]  P. Savage,et al.  Mechanisms imposing the Vβ bias of Vα14 natural killer T cells and consequences for microbial glycolipid recognition , 2006, The Journal of experimental medicine.

[112]  Y. Okamoto,et al.  Combination therapy of in vitro‐expanded natural killer T cells and α‐galactosylceramide‐pulsed antigen‐presenting cells in patients with recurrent head and neck carcinoma , 2009, Cancer science.

[113]  P. Parham MHC class I molecules and kirs in human history, health and survival , 2005, Nature Reviews Immunology.

[114]  H. Kirchner,et al.  Kinetics and organ distribution of allogeneic natural killer lymphocytes transfused into patients suffering from renal cell carcinoma. , 2004, Stem cells and development.

[115]  H. Klingemann,et al.  Infusion of the allogeneic cell line NK-92 in patients with advanced renal cell cancer or melanoma: a phase I trial. , 2008, Cytotherapy.

[116]  G. Altavilla,et al.  Natural killer cells infiltrating human nonsmall‐cell lung cancer are enriched in CD56brightCD16− cells and display an impaired capability to kill tumor cells , 2008, Cancer.

[117]  K. Gagne,et al.  KIR matching in hematopoietic stem cell transplantation. , 2005, Current opinion in immunology.

[118]  F. Christiansen,et al.  Natural killer cell HLA-C epitopes and killer cell immunoglobulin-like receptors both influence outcome of mismatched unrelated donor bone marrow transplants. , 2005, Tissue antigens.

[119]  N. Shastri,et al.  Ligands for the murine NKG2D receptor: expression by tumor cells and activation of NK cells and macrophages , 2000, Nature Immunology.

[120]  Sofia Johansson,et al.  The strength of inhibitory input during education quantitatively tunes the functional responsiveness of individual natural killer cells. , 2009, Blood.

[121]  S. Balk,et al.  Analysis of T cell antigen receptor (TCR) expression by human peripheral blood CD4-8- alpha/beta T cells demonstrates preferential use of several V beta genes and an invariant TCR alpha chain , 1993, The Journal of experimental medicine.

[122]  É. Vivier,et al.  Natural killer cell-based therapies , 2011, F1000 medicine reports.

[123]  T. Mcclanahan,et al.  Retinoic acid early inducible genes define a ligand family for the activating NKG2D receptor in mice. , 2000, Immunity.

[124]  L. Lanier,et al.  “Unlicensed” Natural Killer cells dominate the response to cytomegalovirus infection , 2010, Nature Immunology.

[125]  T. Iizasa,et al.  A Phase I Study of α-Galactosylceramide (KRN7000)–Pulsed Dendritic Cells in Patients with Advanced and Recurrent Non–Small Cell Lung Cancer , 2005, Clinical Cancer Research.

[126]  M. Kronenberg,et al.  Selective ability of mouse CD1 to present glycolipids: alpha-galactosylceramide specifically stimulates V alpha 14+ NK T lymphocytes. , 1998, Journal of immunology.

[127]  A. Poggi,et al.  Cyclosporin A regulates human NK cell apoptosis induced by soluble HLA-I or by target cells. , 2005, Autoimmunity reviews.

[128]  D. Ho,et al.  Enhancement of HIV DNA vaccine immunogenicity by the NKT cell ligand, alpha-galactosylceramide. , 2008, Vaccine.

[129]  M. Kronenberg,et al.  Cutting Edge: IFN-γ Signaling to Macrophages Is Required for Optimal Vα14i NK T/NK Cell Cross-Talk1 , 2005, The Journal of Immunology.

[130]  M. Talpaz,et al.  Long-Term follow-up of recipients of CD8-depleted donor lymphocyte infusions for the treatment of chronic myelogenous leukemia relapsing after allogeneic progenitor cell transplantation. , 2001, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[131]  H. Dombret,et al.  A phase I study of the anti-natural killer inhibitory receptor (KIR) monoclonal antibody (1-7F9, IPH2101) in elderly patients with acute myeloid leukemia (AML). , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[132]  L. Zitvogel,et al.  Natural killer cell–directed therapies: moving from unexpected results to successful strategies , 2008, Nature Immunology.

[133]  山崎 一樹 Induction of NKT cell-specific immune responses in cancer tissues after NKT cell-targeted adoptive immunotherapy , 2010 .

[134]  M. Caligiuri,et al.  Innate or Adaptive Immunity? The Example of Natural Killer Cells , 2011, Science.

[135]  Megan E. McNerney,et al.  A new self: MHC-class-I-independent Natural-killer-cell self-tolerance , 2005, Nature Reviews Immunology.

[136]  A. Telenti,et al.  Critical role for CXCR6 in NK cell-mediated antigen-specific memory to haptens and viruses , 2010, Nature Immunology.

[137]  Marcela R. Uribe,et al.  Rapid natural killer cell recovery determines outcome after T-cell-depleted HLA-identical stem cell transplantation in patients with myeloid leukemias but not with acute lymphoblastic leukemia , 2007, Leukemia.

[138]  C. Craddock,et al.  Durability of responses following donor lymphocyte infusions for patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia , 2000 .

[139]  R. Biassoni,et al.  Identification and Molecular Characterization of Nkp30, a Novel Triggering Receptor Involved in Natural Cytotoxicity Mediated by Human Natural Killer Cells , 1999, The Journal of experimental medicine.

[140]  C. Leemans,et al.  Circulating invariant natural killer T-cell numbers predict outcome in head and neck squamous cell carcinoma: updated analysis with 10-year follow-up. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[141]  D. Raulet,et al.  Oncogenic stress sensed by the immune system: role of natural killer cell receptors , 2009, Nature Reviews Immunology.

[142]  M. Kronenberg,et al.  The unconventional lifestyle of NKT cells , 2002, Nature Reviews Immunology.

[143]  R. Schreiber,et al.  Natural innate and adaptive immunity to cancer. , 2011, Annual review of immunology.

[144]  W. Yokoyama,et al.  MHC class I–deficient natural killer cells acquire a licensed phenotype after transfer into an MHC class I–sufficient environment , 2010, The Journal of experimental medicine.

[145]  D. Blaise,et al.  Current status of reduced-intensity-conditioning allogeneic stem cell transplantation for acute myeloid leukemia. , 2007, Haematologica.

[146]  Katia Perruccio,et al.  Effectiveness of Donor Natural Killer Cell Alloreactivity in Mismatched Hematopoietic Transplants , 2002, Science.

[147]  R. Biassoni,et al.  Receptors for HLA class-I molecules in human natural killer cells. , 1996, Annual review of immunology.

[148]  P. Pandolfi,et al.  The BTB–zinc finger transcriptional regulator PLZF controls the development of invariant natural killer T cell effector functions , 2008, Nature Immunology.

[149]  Tak W. Mak,et al.  Nfil3/E4bp4 is required for the development and maturation of NK cells in vivo , 2009, The Journal of experimental medicine.

[150]  L. Chiche,et al.  The Role of Natural Killer Cells in Sepsis , 2011, Journal of biomedicine & biotechnology.

[151]  R. Storb Allogeneic hematopoietic stem cell transplantation--yesterday, today, and tomorrow. , 2003, Experimental hematology.

[152]  M. Caligiuri,et al.  Preclinical characterization of 1-7F9, a novel human anti-KIR receptor therapeutic antibody that augments natural killer-mediated killing of tumor cells. , 2009, Blood.

[153]  Eric Vivier,et al.  Natural Killer Cell Signaling Pathways , 2004, Science.

[154]  R. Kiessling,et al.  „Natural”︁ killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype , 1975, European journal of immunology.

[155]  M. Martinetti,et al.  Anti-leukemia activity of alloreactive NK cells in KIR ligand-mismatched haploidentical HSCT for pediatric patients: evaluation of the functional role of activating KIR and redefinition of inhibitory KIR specificity. , 2009, Blood.

[156]  J. Wagner,et al.  Good manufacturing practices production of natural killer cells for immunotherapy: a six‐year single‐institution experience , 2007, Transfusion.

[157]  Vrajesh V. Parekh,et al.  Impact of bacteria on the phenotype, functions, and therapeutic activities of invariant NKT cells in mice. , 2008, The Journal of clinical investigation.

[158]  S. Balk,et al.  Selective activation, expansion, and monitoring of human iNKT cells with a monoclonal antibody specific for the TCR α‐chain CDR3 loop , 2008, European journal of immunology.

[159]  A Steinle,et al.  Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. , 1999, Science.

[160]  G. Bubley,et al.  Loss of IFN-γ Production by Invariant NK T Cells in Advanced Cancer1 , 2001, The Journal of Immunology.

[161]  M. Nozue,et al.  Impaired Proliferative Response of Vα24 NKT Cells from Cancer Patients Against α-Galactosylceramide1 , 2002, The Journal of Immunology.

[162]  R. Schots,et al.  A defined donor activating natural killer cell receptor genotype protects against leukemic relapse after related HLA-identical hematopoietic stem cell transplantation , 2005, Leukemia.

[163]  Anneliese O. Speak,et al.  Modulation of human natural killer T cell ligands on TLR-mediated antigen-presenting cell activation , 2007, Proceedings of the National Academy of Sciences.

[164]  Mitchell Kronenberg,et al.  Constitutive Cytokine mRNAs Mark Natural Killer (NK) and NK T Cells Poised for Rapid Effector Function , 2003, The Journal of experimental medicine.

[165]  Transcript signature predicts tissue NK cell content and defines renal cell carcinoma subgroups independent of TNM staging , 2011, Journal of Molecular Medicine.

[166]  L. Bry,et al.  Mechanism of CD1d-restricted natural killer T cell activation during microbial infection , 2003, Nature Immunology.

[167]  Jun Wu,et al.  Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells , 1998, Nature.

[168]  Mark Coles,et al.  The basic leucine zipper transcription factor E4BP4 is essential for natural killer cell development , 2009, Nature Immunology.

[169]  L. Lanier,et al.  Natural Killer Cell Education and Tolerance , 2010, Cell.

[170]  R. Foà,et al.  ATM-ATR-dependent up-regulation of DNAM-1 and NKG2D ligands on multiple myeloma cells by therapeutic agents results in enhanced NK-cell susceptibility and is associated with a senescent phenotype. , 2009, Blood.

[171]  A. Telenti,et al.  Critical role for the chemokine receptor CXCR 6 in NK cell – mediated antigen-specific memory of haptens and viruses , 2010 .

[172]  R. Bouabdallah,et al.  Recovery of Lymphocyte and Dendritic Cell Subsets Following Reduced Intensity Allogeneic Bone Marrow Transplantation , 2002, Hematology.

[173]  M. Smyth,et al.  Innate immunity defines the capacity of antiviral T cells to limit persistent infection , 2010, The Journal of experimental medicine.

[174]  L. Lybarger,et al.  Licensing of natural killer cells by host major histocompatibility complex class I molecules , 2005, Nature.

[175]  T. Yamamura,et al.  A synthetic glycolipid prevents autoimmune encephalomyelitis by inducing TH2 bias of natural killer T cells , 2001, Nature.

[176]  A. Gratwohl,et al.  The EBMT activity survey 2007 with focus on allogeneic HSCT for AML and novel cellular therapies , 2009, Bone Marrow Transplantation.

[177]  Hiroshi Sato,et al.  CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides. , 1997, Science.

[178]  D. Pellicci,et al.  Sequential production of interferon-gamma by NK1.1(+) T cells and natural killer cells is essential for the antimetastatic effect of alpha-galactosylceramide. , 2002, Blood.

[179]  R. Herberman,et al.  Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. I. Distribution of reactivity and specificity , 1975, International journal of cancer.

[180]  B. Beutler Innate immunity: an overview. , 2004, Molecular immunology.

[181]  J. D. Di Santo,et al.  IL-15 availability conditions homeostasis of peripheral natural killer T cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[182]  B. Barlogie,et al.  Infusion of haplo‐identical killer immunoglobulin‐like receptor ligand mismatched NK cells for relapsed myeloma in the setting of autologous stem cell transplantation , 2008, British journal of haematology.

[183]  G. Renukaradhya,et al.  Type I NKT cells protect (and type II NKT cells suppress) the host's innate antitumor immune response to a B-cell lymphoma. , 2008, Blood.

[184]  G. Besra,et al.  Innate and cytokine-driven signals, rather than microbial antigens, dominate in natural killer T cell activation during microbial infection , 2011, The Journal of experimental medicine.

[185]  V. Cerundolo,et al.  Synthetic iNKT cell-agonists as vaccine adjuvants--finding the balance. , 2010, Current opinion in immunology.

[186]  B. Beutler,et al.  Antigen-Specific Cytotoxicity by Invariant NKT Cells In Vivo Is CD95/CD178-Dependent and Is Correlated with Antigenic Potency , 2010, The Journal of Immunology.

[187]  S. Latour,et al.  Essential function for SAP family adaptors in the surveillance of hematopoietic cells by natural killer cells , 2009, Nature Immunology.

[188]  Vrajesh V. Parekh,et al.  Glycolipid antigen induces long-term natural killer T cell anergy in mice. , 2005, The Journal of clinical investigation.

[189]  J. Connors,et al.  Graft-versus-tumor induction with donor leukocyte infusions as primary therapy for patients with malignancies. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[190]  M. Freschi,et al.  iNKT Cells Control Mouse Spontaneous Carcinoma Independently of Tumor-Specific Cytotoxic T Cells , 2010, PloS one.

[191]  C. Verfaillie,et al.  Large scale ex vivo expansion and activation of human natural killer cells for autologous therapy. , 1994, Bone marrow transplantation.

[192]  G. Giaccone,et al.  A phase I study of the natural killer T-cell ligand alpha-galactosylceramide (KRN7000) in patients with solid tumors. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[193]  R. Biassoni,et al.  Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. , 2001, Annual review of immunology.

[194]  A. Nagler,et al.  Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. , 1998, Blood.

[195]  D. Marguet,et al.  Human and mouse killer-cell inhibitory receptors recruit PTP1C and PTP1D protein tyrosine phosphatases. , 1996, Journal of immunology.

[196]  D. Blaise,et al.  Reduced-intensity preparative regimen and allogeneic stem cell transplantation for advanced solid tumors. , 2004, Blood.

[197]  P. Debré,et al.  Infusion of allogeneic natural killer cells in a patient with acute myeloid leukemia in relapse after haploidentical hematopoietic stem cell transplantation , 2011, Transfusion.

[198]  Sustained expansion of NKT cells and antigen-specific T cells after injection of α-galactosyl-ceramide loaded mature dendritic cells in cancer patients , 2005, The Journal of experimental medicine.

[199]  Qian Wang,et al.  Structure of the human activating natural cytotoxicity receptor NKp30 bound to its tumor cell ligand B7-H6 , 2011, The Journal of experimental medicine.

[200]  B. Lindgren,et al.  Allogeneic natural killer cells for refractory lymphoma , 2010, Cancer Immunology, Immunotherapy.

[201]  L. Teyton,et al.  In Vivo Identification of Glycolipid Antigen–Specific T Cells Using Fluorescent Cd1d Tetramers , 2000, The Journal of experimental medicine.

[202]  M. Bonneville,et al.  An Invariant T Cell Receptor α Chain Defines a Novel TAP-independent Major Histocompatibility Complex Class Ib–restricted α/β T Cell Subpopulation in Mammals , 1999, The Journal of experimental medicine.

[203]  R. Welsh,et al.  Natural killer cells act as rheostats modulating antiviral T cells , 2011, Nature.

[204]  R Storb,et al.  Bone-marrow transplantation (first of two parts). , 1975, The New England journal of medicine.

[205]  R. Storb,et al.  Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts. , 1979, The New England journal of medicine.

[206]  M. Martelli,et al.  Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: challenging its predictive value. , 2006, Blood.

[207]  S. Akira,et al.  Toll-like receptors: critical proteins linking innate and acquired immunity , 2001, Nature Immunology.

[208]  É. Vivier,et al.  NK Cell Responsiveness Is Tuned Commensurate with the Number of Inhibitory Receptors for Self-MHC Class I: The Rheostat Model 1 , 2009, The Journal of Immunology.

[209]  N. Segal,et al.  Cross-presentation of Disialoganglioside GD3 to Natural Killer T Cells , 2003, The Journal of experimental medicine.

[210]  N. Nagarajan,et al.  Mechanisms for Glycolipid Antigen-Driven Cytokine Polarization by Vα14i NKT Cells , 2009, The Journal of Immunology.

[211]  U. V. Andrian,et al.  T cell– and B cell–independent adaptive immunity mediated by natural killer cells , 2006, Nature Immunology.

[212]  Mitchell Kronenberg,et al.  Toward an understanding of NKT cell biology: progress and paradoxes. , 2005, Annual review of immunology.

[213]  C. Le,et al.  Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. , 2005, Blood.

[214]  T. Iizasa,et al.  A phase I study of alpha-galactosylceramide (KRN7000)-pulsed dendritic cells in patients with advanced and recurrent non-small cell lung cancer. , 2005, Clinical cancer research : an official journal of the American Association for Cancer Research.

[215]  P. Farnham,et al.  T-bet regulates the terminal maturation and homeostasis of NK and Valpha14i NKT cells. , 2004, Immunity.

[216]  H. Ljunggren,et al.  Selective rejection of H–2-deficient lymphoma variants suggests alternative immune defence strategy , 1986, Nature.

[217]  P. Brodin,et al.  NK cell education: not an on-off switch but a tunable rheostat. , 2009, Trends in immunology.

[218]  K. Kärre How to recongnize a foreign submarine , 1997 .

[219]  D. Middleton,et al.  Human NK cell education by inhibitory receptors for MHC class I. , 2006, Immunity.

[220]  M. Venkataswamy,et al.  Lipid and glycolipid antigens of CD1d-restricted natural killer T cells. , 2010, Seminars in immunology.

[221]  S. Balk,et al.  Direct CD1d-Mediated Stimulation of APC IL-12 Production and Protective Immune Response to Virus Infection In Vivo , 2009, The Journal of Immunology.

[222]  G. Besra,et al.  CD169+ MACROPHAGES PRESENT LIPID ANTIGENS TO MEDIATE EARLY ACTIVATION OF INVARIANT NKT CELLS IN LYMPH NODES , 2010, Nature Immunology.

[223]  J. P. McCoy,et al.  Reduction of GVHD and enhanced antitumor effects after adoptive infusion of alloreactive Ly49-mismatched NK cells from MHC-matched donors. , 2007, Blood.

[224]  É. Vivier,et al.  G-protein-coupled receptors in control of natural killer cell migration. , 2011, Trends in immunology.

[225]  F. Vély,et al.  Natural killer cells in human autoimmune diseases , 2010, Immunology.

[226]  K. Kärre How to recognize a foreign submarine. , 1997, Immunological reviews.

[227]  R. Jaenisch,et al.  MHC class I deficiency: susceptibility to natural killer (NK) cells and impaired NK activity. , 1991, Science.

[228]  P. Cresswell,et al.  Kinetics and Cellular Site of Glycolipid Loading Control the Outcome of Natural Killer T Cell Activation , 2009, Immunity.

[229]  C. Craddock,et al.  Donor KIR genotype has a major influence on the rate of cytomegalovirus reactivation following T-cell replete stem cell transplantation. , 2005, Blood.

[230]  W. Yokoyama,et al.  MHC class I alloantigen specificity of Ly-49+ IL-2-activated natural killer cells , 1992, Nature.

[231]  N. Greenberg,et al.  NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy. , 2008, Immunity.

[232]  M. Cilli,et al.  Human NK cell infusions prolong survival of metastatic human neuroblastoma-bearing NOD/scid mice , 2007, Cancer Immunology, Immunotherapy.

[233]  D. Raulet Roles of the NKG2D immunoreceptor and its ligands , 2003, Nature Reviews Immunology.

[234]  D. Pellicci,et al.  The Elusive NKT Cell Antigen--Is the Search Over? , 2004, Science.

[235]  O. Lantz,et al.  An invariant T cell receptor alpha chain is used by a unique subset of major histocompatibility complex class I-specific CD4+ and CD4-8- T cells in mice and humans , 1994, The Journal of experimental medicine.

[236]  C. Biron,et al.  Elevated natural killer cell-mediated cytotoxicity, plasma interferon, and tumor cell rejection in mice persistently infected with lymphocytic choriomeningitis virus. , 1983, Journal of immunology.

[237]  H. Macdonald,et al.  Cutting edge: influence of the TCR V beta domain on the avidity of CD1d:alpha-galactosylceramide binding by invariant V alpha 14 NKT cells. , 2003, Journal of immunology.

[238]  H. Deeg,et al.  Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation. , 1997, Blood.

[239]  J. Altman,et al.  Mouse CD94/NKG2A Is a Natural Killer Cell Receptor for the Nonclassical Major Histocompatibility Complex (MHC) Class I Molecule Qa-1b , 1998, The Journal of experimental medicine.

[240]  D. Pellicci,et al.  A Natural Killer T (NKT) Cell Developmental Pathway Involving a Thymus-dependent NK1.1−CD4+ CD1d-dependent Precursor Stage , 2002, The Journal of experimental medicine.

[241]  R. Vance,et al.  A subset of natural killer cells achieves self-tolerance without expressing inhibitory receptors specific for self-MHC molecules. , 2005, Blood.

[242]  W. Lehmacher,et al.  Increased Serum Levels of Tumor Necrosis Factor a ! Precede Major Complications of Bone Marrow Transplantation , 2003 .

[243]  É. Vivier,et al.  Human killer cell activatory receptors for MHC class I molecules are included in a multimeric complex expressed by natural killer cells. , 1997, Journal of immunology.

[244]  T. Yamamura,et al.  The clinical implication and molecular mechanism of preferential IL-4 production by modified glycolipid-stimulated NKT cells. , 2004, The Journal of clinical investigation.

[245]  A. Toubert,et al.  Activating KIR genes are associated with CMV reactivation and survival after non-T-cell depleted HLA-identical sibling bone marrow transplantation for malignant disorders , 2006, Bone Marrow Transplantation.

[246]  P. Stein,et al.  CD1d-Expressing Breast Cancer Cells Modulate NKT Cell-Mediated Antitumor Immunity in a Murine Model of Breast Cancer Metastasis , 2011, PloS one.

[247]  W. Yokoyama,et al.  How do natural killer cells find self to achieve tolerance? , 2006, Immunity.

[248]  M. Martelli,et al.  Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. , 1998, The New England journal of medicine.

[249]  Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections , 2005, Nature.

[250]  L. Moretta,et al.  NK cell activating receptors and tumor recognition in humans. , 2006, Current topics in microbiology and immunology.

[251]  W. Held,et al.  Natural Killer Cell Mediated Missing-Self Recognition Can Protect Mice from Primary Chronic Myeloid Leukemia In Vivo , 2011, PloS one.

[252]  D. Neuberg,et al.  CD8+ cell depletion of donor lymphocyte infusions using cd8 monoclonal antibody-coated high-density microparticles (CD8-HDM) after allogeneic hematopoietic stem cell transplantation: a pilot study , 2004, Bone Marrow Transplantation.

[253]  H. Macdonald,et al.  Selective induction of NK cell proliferation and cytotoxicity by activated NKT cells , 2000, European journal of immunology.

[254]  J. Cavenagh,et al.  The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation. , 2002, Blood.

[255]  R. Steinman,et al.  Cross-presentation of glycolipid from tumor cells loaded with α-galactosylceramide leads to potent and long-lived T cell–mediated immunity via dendritic cells , 2007, The Journal of experimental medicine.

[256]  T. Yamamura,et al.  Another view of T cell antigen recognition: cooperative engagement of glycolipid antigens by Va14Ja18 natural T(iNKT) cell receptor [corrected]. , 2003, Journal of immunology.

[257]  H. Ai,et al.  Infusion of HLA-mismatched peripheral blood stem cells improves the outcome of chemotherapy for acute myeloid leukemia in elderly patients. , 2011, Blood.

[258]  H. Mühl,et al.  IL-2 Stimulated but Not Unstimulated NK Cells Induce Selective Disappearance of Peripheral Blood Cells: Concomitant Results to a Phase I/II Study , 2011, PloS one.