IL-15 dendritic cells induce potent activation of natural killer cells: towards the design of an improved dendritic cell vaccine

Heleen Van Acker Eva Lion Sébastien Anguille
Persbericht

IL-15 dendritic cells induce potent activation of natural killer cells: towards the design of an improved dendritic cell vaccine

Het interleukine-15 dendritische celvaccin:

rekrutering van het aangeboren immuunsysteem in de strijd tegen kanker

Sinds de ontdekking van de dendritische cel door Ralph Steinman 40 jaar geleden en de alsmaar groeiende kennis over haar rol in het bestrijden van kanker, staat deze dirigent van het immuunsysteem centraal in de ontwikkeling van kankervaccinatiestrategieën. De Tumorimmunologiegroep van het Laboratorium voor Experimentele Hematologie aan de Universiteit Antwerpen heeft een veelbelovend vaccin ontwikkeld dat in staat is om het verworven immuunsysteem te mobiliseren, om zelf kankercellen te doden en om – aangetoond met dit eindwerk – ook de aangeboren “killercellen” te activeren. Deze bevindingen creëren nieuwe inzichten over hoe het immuunantwoord in kankerpatiënten kan versterkt worden met behulp van dendritische celvaccinatie.

Immuuntherapie, ofwel het aanwenden van het eigen immuunsysteem van de patiënt voor therapeutische doeleinden, is aan een belangrijke opmars bezig binnen de behandeling van kanker en is in toenemende mate een plaats aan het veroveren naast de drie conventionele vormen van kankertherapie: heelkunde, chemotherapie en radiotherapie. Aan de basis van deze therapievorm ligt de kennis dat zowel het aangeboren (eerstelijnsafweer) als het adaptief (verworven) immuunsysteem in staat zijn om kankercellen als lichaamsvreemde cellen te herkennen en te elimineren. Kankercellen kunnen echter ontsnappen aan de controle van het immuunsysteem door zichzelf te “vermommen” zodat ze niet als doelwit herkend worden door de immuuncellen of door actief de werking van het immuunsysteem te blokkeren. Het doel van immuuntherapie is dan ook om de kracht van het antitumoraal immuunantwoord te herstellen of te versterken.

Een veelbelovende vorm van immuuntherapie is vaccinatie met tumorantigeengeladen dendritische cellen (DC). Tumorantigenen zijn lichaamsvreemde of vervormde lichaamseigen moleculen op tumorcellen die afweermechanismen in gang kunnen zetten. Dendritische cellen beschikken over het unieke vermogen om antigenen te verwerken en te presenteren aan T-cellen, de elitetroepen van ons adaptieve immuunsysteem. T-cellen leren dan op die manier om tumorcellen gericht (d.i. antigeenspecifiek) op te sporen en te elimineren.

De concentratie aan DC in de bloedcirculatie is laag waardoor het niet haalbaar is om DC in voldoende hoge aantallen rechtstreeks uit het bloed te isoleren om kankervaccins te bereiden. Daarom worden DC meestal buiten het lichaam gekweekt vanuit monocyten (voorlopercellen van DC) die wel in voldoende hoge aantallen circuleren in het bloed (figuur 1). Deze monocyten kunnen in het laboratorium worden uitgerijpt tot DC, die vervolgens geactiveerd en geladen kunnen worden met één of meer tumorantigenen om T-cellen specifiek te onderwijzen tegen kanker. Na dit DC vaccinbereidingsproces kunnen de cellen opnieuw toegediend worden bij de patiënt.

In de huidige klinische trials wordt hoofdzakelijk gebruik gemaakt van zogenaamde ‘interleukine-4 DC’. Deze studies hebben aangetoond dat DC-vaccinatie veilig is en dat het adaptief immuunsysteem van de patiënt gemobiliseerd kan worden om kankercellen aan te vallen. De groep patiënten die effectief genezen wordt verklaard na interleukine-4 DC-vaccinatie blijft echter beperkt (zelden meer dan 15%), hetgeen de noodzaak onderstreept van een verdere verbetering van de DC-vaccinbereidingsprocedure. Het is in deze context dat de Tumorimmunologiegroep van het Laboratorium voor Experimentele Hematologie van de Universiteit Antwerpen de afgelopen jaren gewerkt heeft aan een nieuw, verbeterd DC-vaccinbereidingsprotocol. Van deze zogenaamde ‘interleukine-15 DC’ is door onze onderzoeksgroep aangetoond dat zij zelf tumorceldodende eigenschappen hebben, in tegenstelling tot de huidige interleukine-4 DC, en dat ze daarnaast eveneens beschikken over een krachtiger vermogen om adaptieve tumorantigeenspecifieke T-cellen te stimuleren.

Tot op heden is er relatief weinig bekend over de capaciteit van DC-vaccins om het aangeboren immuunsysteem, met als centrale spelers de “natural killer” (NK)-cellen, te activeren. NK-cellen beschikken over de belangrijke eigenschap om onderscheid te maken tussen gezonde lichaamseigen cellen en cellen onder fysiologische stress, zoals kankercellen, zonder dat ze hiervoor eerst antigenen moeten leren herkennen. Zoals hun naam al doet vermoeden, kunnen ze deze zieke en lichaamsvreemde cellen ook doden. Met de groeiende kennis over het cruciaal belang van de celdodende en immuunregulerende activiteiten van NK-cellen in de ontwikkeling van antitumoractiviteit, was het doel van deze studie om de effecten van de huidige interleukine-4 DC en de nieuwe interleukine‑15 DC op NK-cellen in vitro (in het laboratorium en niet in de patiënt) te onderzoeken.

De experimenten werden uitgevoerd in een model van acute myeloïde leukemie, een agressieve bloedkanker die een zeer slechte prognose kent ondanks bestaande behandelingen. Eén van de voornaamste redenen hiervan is dat het merendeel van de patiënten – ondanks behandeling met chemotherapie – hervalt. De resultaten van dit laboratoriumonderzoek tonen aan dat NK-cellen beter worden geactiveerd door de alternatieve interleukine-15 DC dan door de klassieke interleukine-4 DC. In een eerste fase werd het aantrekkingsvermogen van NK-cellen door DC geëvalueerd. De mogelijkheid dat cellen in elkaars nabijheid komen is van belang voor het tot stand brengen van celinteracties en daaruitvolgende celactivatie. Onze resultaten tonen aan dat interleukine-15 DC, in tegenstelling tot interleukine-4 DC, NK-cellen effectief kunnen aantrekken. In een tweede fase werden uiterlijke kenmerken die geassocieerd worden met NK-celactivatie opgevolgd voor en na interactie met DC. Hieruit blijkt dat interleukine-4 DC slechts minimale veranderingen veroorzaken bij NK-cellen. Interleukine-15 DC daarentegen, blijken krachtige promotoren te zijn van een gunstig NK-celuiterlijk. Dit wordt weerspiegeld door een verhoogde expressie van activerende receptoren die betrokken zijn bij de vernietiging van leukemiecellen door NK-cellen. In een derde en laatste fase werd de effectieve celdodende capaciteit van NK-cellen na interactie met DC onderzocht. Deze resultaten tonen aan dat NK-cellen na contact met interleukine-15 DC, maar niet met interleukine-4 DC, niet alleen zeer efficiënt leukemiecellen vernietigen, maar ook in staat zijn om tumorcellen te elimineren die anders resistent zijn aan vernietiging door NK-cellen. Bovendien tonen we aan dat de interleukine-15 DC geen ongewenste vernietiging van lichaamseigen cellen veroorzaken, wat zeer belangrijk is in de context van veilige immuuntherapie.

Uit dit thesisonderzoek kunnen we concluderen dat de nieuw ontwikkelde interleukine-15 DC op een veilige en efficiënte manier, naast een T-celstimulerend en direct celdodend vermogen, NK-cellen van het aangeboren immuunsysteem kunnen activeren. Deze bevindingen creëren nieuwe inzichten over hoe het immunantwoord in kankerpatiënten kan versterkt worden met behulp van dendritische celvaccinatie. De resultaten van deze thesis zijn dan ook een zeer belangrijke stap voorwaarts in het verbeteren van de huidige DC-vaccinbereidingsprotocols.

Bibliografie

1.         Smyth MJ, Sullivan LC, Brooks AG, Andrews DM. Non-classical MHC Class I molecules regulating natural killer cell function. Oncoimmunology. 2013;2(3):e23336.

2.         World Health Organisation [internet]. Geneva2013 [updated January 2013; cited 2013 March 2]. Available from: http://www.who.int/mediacentre/factsheets/fs297/en/.

3.         Tallman MS, Gilliland DG, Rowe JM. Drug therapy for acute myeloid leukemia. Blood. 2005;106(4):1154-63.

4.         Smits EL, Berneman ZN, Van Tendeloo VF. Immunotherapy of acute myeloid leukemia: current approaches. The oncologist. 2009;14(3):240-52.

5.         Deschler B, Lubbert M. Acute myeloid leukemia: epidemiology and etiology. Cancer. 2006;107(9):2099-107.

6.         Thein MS, Ershler WB, Jemal A, Yates JW, Baer MR. Outcome of older patients with acute myeloid leukemia: An Analysis of SEER Data Over 3 Decades. Cancer. 2013.

7.         Anguille S, Lion E, Smits E, Berneman ZN, van Tendeloo VF. Dendritic cell vaccine therapy for acute myeloid leukemia: questions and answers. Human vaccines. 2011;7(5):579-84.

8.         Estey E, Dohner H. Acute myeloid leukaemia. Lancet. 2006;368(9550):1894-907.

9.         Roboz GJ. Current treatment of acute myeloid leukemia. Current opinion in oncology. 2012;24(6):711-9.

10.       Zhu X, Ma Y, Liu D. Novel agents and regimens for acute myeloid leukemia: 2009 ASH annual meeting highlights. Journal of hematology & oncology. 2010;3:17.

11.       Al-Mawali A, Gillis D, Lewis I. The role of multiparameter flow cytometry for detection of minimal residual disease in acute myeloid leukemia. American journal of clinical pathology. 2009;131(1):16-26.

12.       van der Pol MA, Pater JM, Feller N, Westra AH, van Stijn A, Ossenkoppele GJ, et al. Functional characterization of minimal residual disease for P-glycoprotein and multidrug resistance protein activity in acute myeloid leukemia. Leukemia. 2001;15(10):1554-63.

13.       Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115(3):453-74.

14.       Kolb HJ. Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood. 2008;112(12):4371-83.

15.       Van Tendeloo VF, Van de Velde A, Van Driessche A, Cools N, Anguille S, Ladell K, et al. Induction of complete and molecular remissions in acute myeloid leukemia by Wilms' tumor 1 antigen-targeted dendritic cell vaccination. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(31):13824-9.

16.       Barrett AJ. Understanding and harnessing the graft-versus-leukaemia effect. British journal of haematology. 2008;142(6):877-88.

17.       Anguille S, Willemen Y, Lion E, Smits EL, Berneman ZN. Dendritic cell vaccination in acute myeloid leukemia. Cytotherapy. 2012;14(6):647-56.

18.       Chan L, Hardwick NR, Guinn BA, Darling D, Gaken J, Galea-Lauri J, et al. An immune edited tumour versus a tumour edited immune system: Prospects for immune therapy of acute myeloid leukaemia. Cancer immunology, immunotherapy : CII. 2006;55(8):1017-24.

19.       Lion E, Willemen Y, Berneman ZN, Van Tendeloo VF, Smits EL. Natural killer cell immune escape in acute myeloid leukemia. Leukemia. 2012;26(9):2019-26.

20.       Morris JC, Waldmann TA. Antibody-based therapy of leukaemia. Expert reviews in molecular medicine. 2009;11:e29.

21.       Rosenberg SA, Restifo NP, Yang JC, Morgan RA, Dudley ME. Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nature reviews Cancer. 2008;8(4):299-308.

22.       Blaser BW, Caligiuri MA. Autologous immune strategies to reduce the risk of leukemic relapse: consideration for IL-15. Best practice & research Clinical haematology. 2006;19(2):281-92.

23.       Anguille S, Lion E, Willemen Y, Van Tendeloo VF, Berneman ZN, Smits EL. Interferon-alpha in acute myeloid leukemia: an old drug revisited. Leukemia. 2011;25(5):739-48.

24.       Anguille S, Van Tendeloo VF, Berneman ZN. Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia. Leukemia. 2012;26(10):2186-96.

25.       Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells. Nature reviews Cancer. 2012;12(4):265-77.

26.       Abbas AK, Lichtman AH, Pillai S. Cellular and Molecular Immunology. sixth ed. Philadelphia: Saunders; 2010.

27.       Van Brussel I, Berneman ZN, Cools N. Optimizing dendritic cell-based immunotherapy: tackling the complexity of different arms of the immune system. Mediators of inflammation. 2012;2012:690643.

28.       Wu L, Liu YJ. Development of dendritic-cell lineages. Immunity. 2007;26(6):741-50.

29.       Hubo M, Trinschek B, Kryczanowsky F, Tuettenberg A, Steinbrink K, Jonuleit H. Costimulatory molecules on immunogenic versus tolerogenic human dendritic cells. Frontiers in immunology. 2013;4:82.

30.       Sabado RL, Bhardwaj N. Dendritic cell immunotherapy. Annals of the New York Academy of Sciences. 2013;1284(1):31-45.

31.       Gerrits JH, Athanassopoulos P, Vaessen LM, Klepper M, Weimar W, van Besouw NM. Peripheral blood manipulation significantly affects the result of dendritic cell monitoring. Transplant immunology. 2007;17(3):169-77.

32.       Figdor CG, de Vries IJ, Lesterhuis WJ, Melief CJ. Dendritic cell immunotherapy: mapping the way. Nature medicine. 2004;10(5):475-80.

33.       Steinman RM, Banchereau J. Taking dendritic cells into medicine. Nature. 2007;449(7161):419-26.

34.       Moretta L, Ferlazzo G, Bottino C, Vitale M, Pende D, Mingari MC, et al. Effector and regulatory events during natural killer-dendritic cell interactions. Immunological reviews. 2006;214:219-28.

35.       Kalinski P, Hilkens CM, Wierenga EA, Kapsenberg ML. T-cell priming by type-1 and type-2 polarized dendritic cells: the concept of a third signal. Immunology today. 1999;20(12):561-7.

36.       Tuyaerts S, Aerts JL, Corthals J, Neyns B, Heirman C, Breckpot K, et al. Current approaches in dendritic cell generation and future implications for cancer immunotherapy. Cancer immunology, immunotherapy : CII. 2007;56(10):1513-37.

37.       Collins M, Ling V, Carreno BM. The B7 family of immune-regulatory ligands. Genome biology. 2005;6(6):223.

38.       Croft M. The role of TNF superfamily members in T-cell function and diseases. Nature reviews Immunology. 2009;9(4):271-85.

39.       Wing K, Yamaguchi T, Sakaguchi S. Cell-autonomous and -non-autonomous roles of CTLA-4 in immune regulation. Trends in immunology. 2011;32(9):428-33.

40.       Anguille S, Smits EL, Cools N, Goossens H, Berneman ZN, Van Tendeloo VF. Short-term cultured, interleukin-15 differentiated dendritic cells have potent immunostimulatory properties. Journal of translational medicine. 2009;7:109.

41.       Gilboa E. DC-based cancer vaccines. The Journal of clinical investigation. 2007;117(5):1195-203.

42.       Massa C, Seliger B. Fast Dendritic Cells Stimulated with Alternative Maturation Mixtures Induce Polyfunctional and Long-Lasting Activation of Innate and Adaptive Effector Cells with Tumor-Killing Capabilities. J Immunol. 2013.

43.       Jonuleit H, Kuhn U, Muller G, Steinbrink K, Paragnik L, Schmitt E, et al. Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions. European journal of immunology. 1997;27(12):3135-42.

44.       Cilloni D, Messa F, Arruga F, Defilippi I, Gottardi E, Fava M, et al. Early prediction of treatment outcome in acute myeloid leukemia by measurement of WT1 transcript levels in peripheral blood samples collected after chemotherapy. Haematologica. 2008;93(6):921-4.

45.       Van Tendeloo VF, Ponsaerts P, Lardon F, Nijs G, Lenjou M, Van Broeckhoven C, et al. Highly efficient gene delivery by mRNA electroporation in human hematopoietic cells: superiority to lipofection and passive pulsing of mRNA and to electroporation of plasmid cDNA for tumor antigen loading of dendritic cells. Blood. 2001;98(1):49-56.

46.       National Library of Medicine [internet]. Rockville Pike, Bethesda, USA [updated June 3 2013; cited 2013 June 5]. Available from: http://www.clinicaltrials.gov/ct2/show/NCT01686334?term=acute+myeloid+l….

47.       Lee JJ, Kook H, Park MS, Nam JH, Choi BH, Song WH, et al. Immunotherapy using autologous monocyte-derived dendritic cells pulsed with leukemic cell lysates for acute myeloid leukemia relapse after autologous peripheral blood stem cell transplantation. Journal of clinical apheresis. 2004;19(2):66-70.

48.       Li L, Giannopoulos K, Reinhardt P, Tabarkiewicz J, Schmitt A, Greiner J, et al. Immunotherapy for patients with acute myeloid leukemia using autologous dendritic cells generated from leukemic blasts. International journal of oncology. 2006;28(4):855-61.

49.       Kitawaki T, Kadowaki N, Fukunaga K, Kasai Y, Maekawa T, Ohmori K, et al. A phase I/IIa clinical trial of immunotherapy for elderly patients with acute myeloid leukaemia using dendritic cells co-pulsed with WT1 peptide and zoledronate. British journal of haematology. 2011;153(6):796-9.

50.       Roddie H, Klammer M, Thomas C, Thomson R, Atkinson A, Sproul A, et al. Phase I/II study of vaccination with dendritic-like leukaemia cells for the immunotherapy of acute myeloid leukaemia. British journal of haematology. 2006;133(2):152-7.

51.       Van Driessche A, Van de Velde AL, Nijs G, Braeckman T, Stein B, De Vries JM, et al. Clinical-grade manufacturing of autologous mature mRNA-electroporated dendritic cells and safety testing in acute myeloid leukemia patients in a phase I dose-escalation clinical trial. Cytotherapy. 2009;11(5):653-68.

52.       Jakobisiak M, Golab J, Lasek W. Interleukin 15 as a promising candidate for tumor immunotherapy. Cytokine & growth factor reviews. 2011;22(2):99-108.

53.       Ben Ahmed M, Belhadj Hmida N, Moes N, Buyse S, Abdeladhim M, Louzir H, et al. IL-15 renders conventional lymphocytes resistant to suppressive functions of regulatory T cells through activation of the phosphatidylinositol 3-kinase pathway. J Immunol. 2009;182(11):6763-70.

54.       Lucas M, Schachterle W, Oberle K, Aichele P, Diefenbach A. Dendritic cells prime natural killer cells by trans-presenting interleukin 15. Immunity. 2007;26(4):503-17.

55.       Mortier E, Woo T, Advincula R, Gozalo S, Ma A. IL-15Ralpha chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation. The Journal of experimental medicine. 2008;205(5):1213-25.

56.       Harris KM. Monocytes differentiated with GM-CSF and IL-15 initiate Th17 and Th1 responses that are contact-dependent and mediated by IL-15. Journal of leukocyte biology. 2011;90(4):727-34.

57.       Smits EL, Ponsaerts P, Berneman ZN, Van Tendeloo VF. The use of TLR7 and TLR8 ligands for the enhancement of cancer immunotherapy. The oncologist. 2008;13(8):859-75.

58.       Lion E, Anguille S, Berneman ZN, Smits EL, Van Tendeloo VF. Poly(I:C) enhances the susceptibility of leukemic cells to NK cell cytotoxicity and phagocytosis by DC. PloS one. 2011;6(6):e20952.

59.       Schreibelt G, Tel J, Sliepen KH, Benitez-Ribas D, Figdor CG, Adema GJ, et al. Toll-like receptor expression and function in human dendritic cell subsets: implications for dendritic cell-based anti-cancer immunotherapy. Cancer immunology, immunotherapy : CII. 2010;59(10):1573-82.

60.       Smits EL, Cools N, Lion E, Van Camp K, Ponsaerts P, Berneman ZN, et al. The Toll-like receptor 7/8 agonist resiquimod greatly increases the immunostimulatory capacity of human acute myeloid leukemia cells. Cancer immunology, immunotherapy : CII. 2010;59(1):35-46.

61.       Burdek M, Spranger S, Wilde S, Frankenberger B, Schendel DJ, Geiger C. Three-day dendritic cells for vaccine development: antigen uptake, processing and presentation. Journal of translational medicine. 2010;8:90.

62.       Anguille S, Lion E, Tel J, de Vries IJ, Coudere K, Fromm PD, et al. Interleukin-15-induced CD56(+) myeloid dendritic cells combine potent tumor antigen presentation with direct tumoricidal potential. PloS one. 2012;7(12):e51851.

63.       Lion E, Smits EL, Berneman ZN, Van Tendeloo VF. NK cells: key to success of DC-based cancer vaccines? The oncologist. 2012;17(10):1256-70.

64.       De Maria A, Bozzano F, Cantoni C, Moretta L. Revisiting human natural killer cell subset function revealed cytolytic CD56(dim)CD16+ NK cells as rapid producers of abundant IFN-gamma on activation. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(2):728-32.

65.       Wehner R, Dietze K, Bachmann M, Schmitz M. The bidirectional crosstalk between human dendritic cells and natural killer cells. Journal of innate immunity. 2011;3(3):258-63.

66.       Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends in immunology. 2001;22(11):633-40.

67.       Poli A, Michel T, Theresine M, Andres E, Hentges F, Zimmer J. CD56bright natural killer (NK) cells: an important NK cell subset. Immunology. 2009;126(4):458-65.

68.       Gregoire C, Chasson L, Luci C, Tomasello E, Geissmann F, Vivier E, et al. The trafficking of natural killer cells. Immunological reviews. 2007;220:169-82.

69.       Fauriat C, Long EO, Ljunggren HG, Bryceson YT. Regulation of human NK-cell cytokine and chemokine production by target cell recognition. Blood. 2010;115(11):2167-76.

70.       Spits H, Lanier LL. Natural killer or dendritic: what's in a name? Immunity. 2007;26(1):11-6.

71.       Zanoni I, Granucci F, Foti M, Ricciardi-Castagnoli P. Self-tolerance, dendritic cell (DC)-mediated activation and tissue distribution of natural killer (NK) cells. Immunology letters. 2007;110(1):6-17.

72.       Benjamin JE, Gill S, Negrin RS. Biology and clinical effects of natural killer cells in allogeneic transplantation. Current opinion in oncology. 2010;22(2):130-7.

73.       Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nature immunology. 2008;9(5):503-10.

74.       Raulet DH. Interplay of natural killer cells and their receptors with the adaptive immune response. Nature immunology. 2004;5(10):996-1002.

75.       Yokoyama WM, Kim S. Licensing of natural killer cells by self-major histocompatibility complex class I. Immunological reviews. 2006;214:143-54.

76.       Varchetta S, Oliviero B, Mavilio D, Mondelli MU. Different combinations of cytokines and activating receptor stimuli are required for human natural killer cell functional diversity. Cytokine. 2013.

77.       Byrd A, Hoffmann SC, Jarahian M, Momburg F, Watzl C. Expression analysis of the ligands for the Natural Killer cell receptors NKp30 and NKp44. PloS one. 2007;2(12):e1339.

78.       Girart MV, Fuertes MB, Domaica CI, Rossi LE, Zwirner NW. Engagement of TLR3, TLR7, and NKG2D regulate IFN-gamma secretion but not NKG2D-mediated cytotoxicity by human NK cells stimulated with suboptimal doses of IL-12. J Immunol. 2007;179(6):3472-9.

79.       Kato N, Tanaka J, Sugita J, Toubai T, Miura Y, Ibata M, et al. Regulation of the expression of MHC class I-related chain A, B (MICA, MICB) via chromatin remodeling and its impact on the susceptibility of leukemic cells to the cytotoxicity of NKG2D-expressing cells. Leukemia. 2007;21(10):2103-8.

80.       Walzer T, Dalod M, Robbins SH, Zitvogel L, Vivier E. Natural-killer cells and dendritic cells: "l'union fait la force". Blood. 2005;106(7):2252-8.

81.       Jinushi M, Takehara T, Kanto T, Tatsumi T, Groh V, Spies T, et al. Critical role of MHC class I-related chain A and B expression on IFN-alpha-stimulated dendritic cells in NK cell activation: impairment in chronic hepatitis C virus infection. J Immunol. 2003;170(3):1249-56.

82.       Wai LE, Garcia JA, Martinez OM, Krams SM. Distinct roles for the NK cell-activating receptors in mediating interactions with dendritic cells and tumor cells. J Immunol. 2011;186(1):222-9.

83.       Ferlazzo G, Pack M, Thomas D, Paludan C, Schmid D, Strowig T, et al. Distinct roles of IL-12 and IL-15 in human natural killer cell activation by dendritic cells from secondary lymphoid organs. Proceedings of the National Academy of Sciences of the United States of America. 2004;101(47):16606-11.

84.       Ferlazzo G, Munz C. Dendritic cell interactions with NK cells from different tissues. Journal of clinical immunology. 2009;29(3):265-73.

85.       Smits EL, Lee C, Hardwick N, Brooks S, Van Tendeloo VF, Orchard K, et al. Clinical evaluation of cellular immunotherapy in acute myeloid leukaemia. Cancer immunology, immunotherapy : CII. 2011;60(6):757-69.

86.       Ruggeri L, Mancusi A, Burchielli E, Aversa F, Martelli MF, Velardi A. Natural killer cell alloreactivity in allogeneic hematopoietic transplantation. Current opinion in oncology. 2007;19(2):142-7.

87.       Waldhauer I, Steinle A. NK cells and cancer immunosurveillance. Oncogene. 2008;27(45):5932-43.

88.       Costello RT, Fauriat C, Sivori S, Marcenaro E, Olive D. NK cells: innate immunity against hematological malignancies? Trends in immunology. 2004;25(6):328-33.

89.       Dubsky P, Saito H, Leogier M, Dantin C, Connolly JE, Banchereau J, et al. IL-15-induced human DC efficiently prime melanoma-specific naive CD8+ T cells to differentiate into CTL. European journal of immunology. 2007;37(6):1678-90.

90.       Hardy MY, Kassianos AJ, Vulink A, Wilkinson R, Jongbloed SL, Hart DN, et al. NK cells enhance the induction of CTL responses by IL-15 monocyte-derived dendritic cells. Immunology and cell biology. 2009;87(8):606-14.

91.       Van Elssen CH, Vanderlocht J, Frings PW, Senden-Gijsbers BL, Schnijderberg MC, van Gelder M, et al. Klebsiella pneumoniae-triggered DC recruit human NK cells in a CCR5-dependent manner leading to increased CCL19-responsiveness and activation of NK cells. European journal of immunology. 2010;40(11):3138-49.

92.       Vujanovic L, Szymkowski DE, Alber S, Watkins SC, Vujanovic NL, Butterfield LH. Virally infected and matured human dendritic cells activate natural killer cells via cooperative activity of plasma membrane-bound TNF and IL-15. Blood. 2010;116(4):575-83.

93.       Rahman M. Introduction to Flow Cytometry. United Kingdom: MorphoSys UK Ltd; 2009.

94.       Shapiro HM. Practical Flow Cytometry. fourth ed. New Jersey: John Wiley & Sons. Inc. ; 2003.

95.       Vermes I, Haanen C, Reutelingsperger C. Flow cytometry of apoptotic cell death. Journal of immunological methods. 2000;243(1-2):167-90.

96.       Overton WR. Modified histogram subtraction technique for analysis of flow cytometry data. Cytometry. 1988;9(6):619-26.

97.       Caligiuri MA. Human natural killer cells. Blood. 2008;112(3):461-9.

98.       Seidel UJ, Schlegel P, Lang P. Natural killer cell mediated antibody-dependent cellular cytotoxicity in tumor immunotherapy with therapeutic antibodies. Frontiers in immunology. 2013;4:76.

99.       Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nature medicine. 2004;10(9):909-15.

100.     Vujanovic L, Ballard W, Thorne SH, Vujanovic NL, Butterfield LH. Adenovirus-engineered human dendritic cells induce natural killer cell chemotaxis via CXCL8/IL-8 and CXCL10/IP-10. Oncoimmunology. 2012;1(4):448-57.

101.     Liu C, Lou Y, Lizee G, Qin H, Liu S, Rabinovich B, et al. Plasmacytoid dendritic cells induce NK cell-dependent, tumor antigen-specific T cell cross-priming and tumor regression in mice. The Journal of clinical investigation. 2008;118(3):1165-75.

102.     Gil M, Park SJ, Chung YS, Park CS. Interleukin-15 enhances proliferation and chemokine secretion of human follicular dendritic cells. Immunology. 2010;130(4):536-44.

103.     Saikh KU, Khan AS, Kissner T, Ulrich RG. IL-15-induced conversion of monocytes to mature dendritic cells. Clinical and experimental immunology. 2001;126(3):447-55.

104.     Gustafsson K, Ingelsten M, Bergqvist L, Nystrom J, Andersson B, Karlsson-Parra A. Recruitment and activation of natural killer cells in vitro by a human dendritic cell vaccine. Cancer research. 2008;68(14):5965-71.

105.     Siddiqui N, Hope J. Differential recruitment and activation of natural killer cell sub-populations by Mycobacterium bovis-infected dendritic cells. European journal of immunology. 2013;43(1):159-69.

106.     Persson CM, Chambers BJ. Plasmacytoid dendritic cell-induced migration and activation of NK cells in vivo. European journal of immunology. 2010;40(8):2155-64.

107.     Ahonen CL, Gibson SJ, Smith RM, Pederson LK, Lindh JM, Tomai MA, et al. Dendritic cell maturation and subsequent enhanced T-cell stimulation induced with the novel synthetic immune response modifier R-848. Cellular immunology. 1999;197(1):62-72.

108.     Jensen SS, Gad M. Differential induction of inflammatory cytokines by dendritic cells treated with novel TLR-agonist and cytokine based cocktails: targeting dendritic cells in autoimmunity. J Inflamm (Lond). 2010;7:37.

109.     Vitale M, Della Chiesa M, Carlomagno S, Romagnani C, Thiel A, Moretta L, et al. The small subset of CD56brightCD16- natural killer cells is selectively responsible for both cell proliferation and interferon-gamma production upon interaction with dendritic cells. European journal of immunology. 2004;34(6):1715-22.

110.     Osada T, Clay T, Hobeika A, Lyerly HK, Morse MA. NK cell activation by dendritic cell vaccine: a mechanism of action for clinical activity. Cancer immunology, immunotherapy : CII. 2006;55(9):1122-31.

111.     Bontkes HJ, Kramer D, Ruizendaal JJ, Meijer CJ, Hooijberg E. Tumor associated antigen and interleukin-12 mRNA transfected dendritic cells enhance effector function of natural killer cells and antigen specific T-cells. Clin Immunol. 2008;127(3):375-84.

112.     Loza MJ, Perussia B. The IL-12 signature: NK cell terminal CD56+high stage and effector functions. J Immunol. 2004;172(1):88-96.

113.     Marquez ME, Millet C, Stekman H, Conesa A, Deglesne PA, Toro F, et al. CD16 cross-linking induces increased expression of CD56 and production of IL-12 in peripheral NK cells. Cellular immunology. 2010;264(1):86-92.

114.     Pende D, Spaggiari GM, Marcenaro S, Martini S, Rivera P, Capobianco A, et al. Analysis of the receptor-ligand interactions in the natural killer-mediated lysis of freshly isolated myeloid or lymphoblastic leukemias: evidence for the involvement of the Poliovirus receptor (CD155) and Nectin-2 (CD112). Blood. 2005;105(5):2066-73.

115.     Fauriat C, Just-Landi S, Mallet F, Arnoulet C, Sainty D, Olive D, et al. Deficient expression of NCR in NK cells from acute myeloid leukemia: Evolution during leukemia treatment and impact of leukemia cells in NCRdull phenotype induction. Blood. 2007;109(1):323-30.

116.     Costello RT, Sivori S, Marcenaro E, Lafage-Pochitaloff M, Mozziconacci MJ, Reviron D, et al. Defective expression and function of natural killer cell-triggering receptors in patients with acute myeloid leukemia. Blood. 2002;99(10):3661-7.

117.     Boyiadzis M, Memon S, Carson J, Allen K, Szczepanski MJ, Vance BA, et al. Up-regulation of NK cell activating receptors following allogeneic hematopoietic stem cell transplantation under a lymphodepleting reduced intensity regimen is associated with elevated IL-15 levels. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2008;14(3):290-300.

118.     Szczepanski MJ, Szajnik M, Welsh A, Whiteside TL, Boyiadzis M. Blast-derived microvesicles in sera from patients with acute myeloid leukemia suppress natural killer cell function via membrane-associated transforming growth factor-beta1. Haematologica. 2011;96(9):1302-9.

119.     Mailliard RB, Son YI, Redlinger R, Coates PT, Giermasz A, Morel PA, et al. Dendritic cells mediate NK cell help for Th1 and CTL responses: two-signal requirement for the induction of NK cell helper function. J Immunol. 2003;171(5):2366-73.

120.     Lion E, Smits EL, Berneman ZN, Van Tendeloo VF. Quantification of IFN-gamma produced by human purified NK cells following tumor cell stimulation: comparison of three IFN-gamma assays. Journal of immunological methods. 2009;350(1-2):89-96.

121.     Lion E, Smits EL, Berneman ZN, Van Tendeloo VF. Acute myeloid leukemic cell lines loaded with synthetic dsRNA trigger IFN-gamma secretion by human NK cells. Leukemia research. 2009;33(4):539-46.

122.     Gerosa F, Gobbi A, Zorzi P, Burg S, Briere F, Carra G, et al. The reciprocal interaction of NK cells with plasmacytoid or myeloid dendritic cells profoundly affects innate resistance functions. J Immunol. 2005;174(2):727-34.

123.     Boullart AC, Aarntzen EH, Verdijk P, Jacobs JF, Schuurhuis DH, Benitez-Ribas D, et al. Maturation of monocyte-derived dendritic cells with Toll-like receptor 3 and 7/8 ligands combined with prostaglandin E2 results in high interleukin-12 production and cell migration. Cancer immunology, immunotherapy : CII. 2008;57(11):1589-97.

124.     Muthuswamy R, Mueller-Berghaus J, Haberkorn U, Reinhart TA, Schadendorf D, Kalinski P. PGE(2) transiently enhances DC expression of CCR7 but inhibits the ability of DCs to produce CCL19 and attract naive T cells. Blood. 2010;116(9):1454-9.

125.     Van Elssen CH, Vanderlocht J, Oth T, Senden-Gijsbers BL, Germeraad WT, Bos GM. Inflammation-restraining effects of prostaglandin E2 on natural killer-dendritic cell (NK-DC) interaction are imprinted during DC maturation. Blood. 2011;118(9):2473-82.

126.     Roothans D, Smits E, Lion E, Tel J, Anguille S. CD56 marks human dendritic cell subsets with cytotoxic potential. Oncoimmunology. 2013;2(2):e23037.

127.     Shi J, Ikeda K, Fujii N, Kondo E, Shinagawa K, Ishimaru F, et al. Activated human umbilical cord blood dendritic cells kill tumor cells without damaging normal hematological progenitor cells. Cancer science. 2005;96(2):127-33.

128.     Manna PP, Mohanakumar T. Human dendritic cell mediated cytotoxicity against breast carcinoma cells in vitro. Journal of leukocyte biology. 2002;72(2):312-20.

129.     Fernandez NC FC, Crépineau F, Angevin E, Vivier E, Zitvogel L. Dendritic cells (DC) promote natural killer (NK) cell functions: dynamics of the human DUNK cell cross talk. Eur Cytokine Netw. 2002;13(1):17-27.

130.     Amakata Y, Fujiyama Y, Andoh A, Hodohara K, Bamba T. Mechanism of NK cell activation induced by coculture with dendritic cells derived from peripheral blood monocytes. Clinical and experimental immunology. 2001;124(2):214-22.

131.     Pallandre JR, Krzewski K, Bedel R, Ryffel B, Caignard A, Rohrlich PS, et al. Dendritic cell and natural killer cell cross-talk: a pivotal role of CX3CL1 in NK cytoskeleton organization and activation. Blood. 2008;112(12):4420-4.

132.     Pende D, Castriconi R, Romagnani P, Spaggiari GM, Marcenaro S, Dondero A, et al. Expression of the DNAM-1 ligands, Nectin-2 (CD112) and poliovirus receptor (CD155), on dendritic cells: relevance for natural killer-dendritic cell interaction. Blood. 2006;107(5):2030-6.

133.     Mortier E, Quemener A, Vusio P, Lorenzen I, Boublik Y, Grotzinger J, et al. Soluble interleukin-15 receptor alpha (IL-15R alpha)-sushi as a selective and potent agonist of IL-15 action through IL-15R beta/gamma. Hyperagonist IL-15 x IL-15R alpha fusion proteins. The Journal of biological chemistry. 2006;281(3):1612-9.

134.     Harris KM. Monocytes differentiated with GM-CSF and IL-15 initiate Th17 and Th1 responses that are contact-dependent and mediated by IL-15. Journal of leukocyte biology. 2011;90(4):727-34.

135.     Dubois S, Patel HJ, Zhang M, Waldmann TA, Muller JR. Preassociation of IL-15 with IL-15R alpha-IgG1-Fc enhances its activity on proliferation of NK and CD8+/CD44high T cells and its antitumor action. J Immunol. 2008;180(4):2099-106.

136.     Waldmann TA, Dubois S, Tagaya Y. Contrasting roles of IL-2 and IL-15 in the life and death of lymphocytes: implications for immunotherapy. Immunity. 2001;14(2):105-10.

Universiteit of Hogeschool
Master of Science in de geneesmiddelenontwikkeling: apotheker
Publicatiejaar
2013
Kernwoorden
Share this on: