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Haploidentical Haematopoietic Stem Cell Transplantation: Role of NK Cells and Effect of Cytomegalovirus Infections

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Natural Killer Cells

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 395))

Abstract

Natural killer cells play an important role in the immune responses against cancer and viral infections. In addition, NK cells have been shown to exert a key role in haploidentical hematopoietic stem cell (HSC) transplantation for the therapy of high-risk leukemias. The anti-leukemia effect is mostly related to the presence of “alloreactive” NK cells, i.e., mature KIR+ NK cells that express inhibitory KIR mismatched with HLA class I (KIR-L) of the patient. In addition, an important role is played by certain activating KIR (primarily, but not only, KIR2DS1) upon interaction with their HLA class I ligand (C2 alleles). In general, the presence of activating KIR correlates with a better prognosis. Beside the infusion of “pure” CD34+ cells, a novel protocol has been recently developed in which depletion of αβ T cells and CD19+ B cells makes it possible to infuse into the patient, together with donor CD34+ HSCs, important effector cells including mature PB NK cells and γδ T cells. Recent studies revealed that cytomegalovirus (CMV) infection/reactivation may induce rapid NK cell maturation and greatly influence the NK receptor repertoire. The remarkable expansion of a subset expressing the activating receptor NKG2C, together with a more efficient virus-specific effector response after rechallenge with CMV (i.e., antigen specificity), and the longevity of the expanded population are all features consistent with an adaptive type of response and support the notion of a memory-like activity of NK cells.

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References

  • Airoldi I, Bertaina A, Prigione I, Zorzoli A, Pagliara D, Cocco C et al (2015) Gammadelta T cell reconstitution after HLA-haploidentical hematopoietic transplantation depleted of TCR-alphabeta+/CD19+ lymphocytes. Blood. doi:10.1182/blood-2014-09-599423

    PubMed Central  PubMed  Google Scholar 

  • Arase H, Mocarski ES, Campbell AE, Hill AB, Lanier LL (2002) Direct recognition of cytomegalovirus by activating and inhibitory NK cell receptors. Science 296(5571):1323–1326. doi:10.1126/science.1070884

    Article  CAS  PubMed  Google Scholar 

  • Aversa F, Tabilio A, Terenzi A, Velardi A, Falzetti F, Giannoni C et al (1994) Successful engraftment of T-cell-depleted haploidentical “three-loci” incompatible transplants in leukemia patients by addition of recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells to bone marrow inoculum. Blood 84(11):3948–3955

    CAS  PubMed  Google Scholar 

  • Aversa F, Tabilio A, Velardi A, Cunningham I, Terenzi A, Falzetti F et al (1998) Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. New Engl J Med 339(17):1186–1193. doi:10.1056/NEJM199810223391702

    Article  CAS  PubMed  Google Scholar 

  • Benson DM Jr, Bakan CE, Zhang S, Collins SM, Liang J, Srivastava S et al (2011) IPH2101, a novel anti-inhibitory KIR antibody, and lenalidomide combine to enhance the natural killer cell versus multiple myeloma effect. Blood 118(24):6387–6391. doi:10.1182/blood-2011-06-360255

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bertaina A, Merli P, Rutella S, Pagliara D, Bernardo ME, Masetti R et al (2014) HLA-haploidentical stem cell transplantation after removal of alphabeta+ T and B cells in children with nonmalignant disorders. Blood 124(5):822–826. doi:10.1182/blood-2014-03-563817

    Article  CAS  PubMed  Google Scholar 

  • Beziat V, Liu LL, Malmberg JA, Ivarsson MA, Sohlberg E, Bjorklund AT et al (2013) NK cell responses to cytomegalovirus infection lead to stable imprints in the human KIR repertoire and involve activating KIRs. Blood 121(14):2678–2688. doi:blood-2012-10-459545 [pii] 10.1182/blood-2012-10-459545

  • Beziat V, Dalgard O, Asselah T, Halfon P, Bedossa P, Boudifa A et al (2012) CMV drives clonal expansion of NKG2C+ NK cells expressing self-specific KIRs in chronic hepatitis patients. Eur J Immunol 42(2):447–457. doi:10.1002/eji.201141826

    Article  CAS  PubMed  Google Scholar 

  • Bjorkstrom NK, Lindgren T, Stoltz M, Fauriat C, Braun M, Evander M et al (2011) Rapid expansion and long-term persistence of elevated NK cell numbers in humans infected with hantavirus. J Exp Med 208(1):13–21. doi:jem.20100762 [pii] 10.1084/jem.20100762

  • Braud VM, Allan DSJ, O’Callaghan CA, Soderstrom K, D’Andrea A, Ogg GS et al (1998) HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature 391(6669):795–799

    Article  CAS  PubMed  Google Scholar 

  • Brodin P, Karre K, Hoglund P (2009) NK cell education: not an on-off switch but a tunable rheostat. Trends Immunol 30(4):143–149. doi:S1471-4906(09)00039-8 [pii] 10.1016/j.it.2009.01.006

  • Caligiuri MA (2008) Human natural killer cells. Blood 112(3):461–469. doi:10.1182/blood-2007-09-077438

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Carrega P, Ferlazzo G (2012) Natural killer cell distribution and trafficking in human tissues. Front Immunol 3:347. doi:10.3389/fimmu.2012.00347

    Article  PubMed Central  PubMed  Google Scholar 

  • Carrega P, Bonaccorsi I, Di Carlo E, Morandi B, Paul P, Rizzello V et al (2014) CD56(bright)perforin(low) noncytotoxic human NK cells are abundant in both healthy and neoplastic solid tissues and recirculate to secondary lymphoid organs via afferent lymph. J Immunol 192(8):3805–3815. doi:10.4049/jimmunol.1301889

    Article  CAS  PubMed  Google Scholar 

  • Cheng M, Chen Y, Xiao W, Sun R, Tian Z (2013) NK cell-based immunotherapy for malignant diseases. Cell Mol Immunol 10(3):230–252. doi:10.1038/cmi.2013.10

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chewning JH, Gudme CN, Hsu KC, Selvakumar A, Dupont B (2007) KIR2DS1-positive NK cells mediate alloresponse against the C2 HLA-KIR ligand group in vitro. J Immunol 179(2):854–868. doi:179/2/854 [pii]

    Google Scholar 

  • Cook M, Briggs D, Craddock C, Mahendra P, Milligan D, Fegan C et al (2006) Donor KIR genotype has a major influence on the rate of cytomegalovirus reactivation following T-cell replete stem cell transplantation. Blood 107(3):1230–1232. doi:2005-03-1039 [pii] 10.1182/blood-2005-03-1039

  • Cooper MA, Fehniger TA, Caligiuri MA (2001) The biology of human natural killer-cell subsets. Trends Immunol 22(11):633–640

    Article  CAS  PubMed  Google Scholar 

  • Costa-Garcia M, Vera A, Moraru M, Vilches C, Lopez-Botet M, Muntasell A (2015) Antibody-Mediated Response of NKG2Cbright NK Cells against Human Cytomegalovirus. J Immunol 194(6):2715–2724. doi:10.4049/jimmunol.1402281

    Article  CAS  PubMed  Google Scholar 

  • Della Chiesa M, Falco M, Podesta M, Locatelli F, Moretta L, Frassoni F et al (2012) Phenotypic and functional heterogeneity of human NK cells developing after umbilical cord blood transplantation: a role for human cytomegalovirus? Blood 119(2):399–410. doi:blood-2011-08-372003 [pii] 10.1182/blood-2011-08-372003

  • Della Chiesa M, Falco M, Muccio L, Bertaina A, Locatelli F, Moretta A (2013) Impact of CMV Infection on NK Cell Development and Function after HSCT. Front Immunol 4:458. doi:10.3389/fimmu.2013.00458

  • Della Chiesa M, Falco M, Bertaina A, Muccio L, Alicata C, Frassoni F et al (2014) Human cytomegalovirus infection promotes rapid maturation of NK cells expressing activating killer Ig-like receptor in patients transplanted with NKG2C-/- umbilical cord blood. J Immunol 192(4):1471–1479. doi:10.4049/jimmunol.1302053

  • Di Bona D, Scafidi V, Plaia A, Colomba C, Nuzzo D, Occhino C et al (2014) HLA and killer cell immunoglobulin-like receptors influence the natural course of CMV infection. J Infect Dis 210(7):1083–1089. doi:10.1093/infdis/jiu226

    Article  PubMed  Google Scholar 

  • Elmaagacli AH, Steckel NK, Koldehoff M, Hegerfeldt Y, Trenschel R, Ditschkowski M et al (2011) Early human cytomegalovirus replication after transplant is associated with a decreased relapse-risk: evidence for a putative virus-versus-leukemia effect AML patients. Blood. doi:blood-2010-08-304121 [pii] 10.1182/blood-2010-08-304121

  • Foley B, Cooley S, Verneris MR, Pitt M, Curtsinger J, Luo X et al (2011) Cytomegalovirus reactivation after allogeneic transplantation promotes a lasting increase in educated NKG2C+ natural killer cells with potent function. Blood. doi:blood-2011-10-386995 [pii] 10.1182/blood-2011-10-386995

  • Foley B, Cooley S, Verneris MR, Curtsinger J, Luo X, Waller EK et al (2012) Human cytomegalovirus (CMV)-induced memory-like NKG2C(+) NK cells are transplantable and expand in vivo in response to recipient CMV antigen. J Immunol 189(10):5082–5088. doi:jimmunol.1201964 [pii] 10.4049/jimmunol.1201964

  • Foley B, Felices M, Cichocki F, Cooley S, Verneris MR, Miller JS (2014) The biology of NK cells and their receptors affects clinical outcomes after hematopoietic cell transplantation (HCT). Immunol Rev 258(1):45–63. doi:10.1111/imr.12157

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gleason MK, Ross JA, Warlick ED, Lund TC, Verneris MR, Wiernik A et al (2014) CD16xCD33 bispecific killer cell engager (BiKE) activates NK cells against primary MDS and MDSC CD33+ targets. Blood 123(19):3016–3026. doi:10.1182/blood-2013-10-533398

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gonzalez A, Schmitter K, Hirsch HH, Garzoni C, van Delden C, Boggian K et al (2014) KIR-associated protection from CMV replication requires pre-existing immunity: a prospective study in solid organ transplant recipients. Genes Immun 15(7):495–499. doi:10.1038/gene.2014.39

    Article  CAS  PubMed  Google Scholar 

  • Graef T, Moesta AK, Norman PJ, Abi-Rached L, Vago L, Older Aguilar AM et al (2009) KIR2DS4 is a product of gene conversion with KIR3DL2 that introduced specificity for HLA-A*11 while diminishing avidity for HLA-C. J Exp Med 206(11):2557–2572. doi:jem.20091010 [pii] 10.1084/jem.20091010

  • Green ML, Leisenring WM, Xie H, Walter RB, Mielcarek M, Sandmaier BM et al (2013) CMV reactivation after allogeneic HCT and relapse risk: evidence for early protection in acute myeloid leukemia. Blood 122(7):1316–1324. doi:10.1182/blood-2013-02-487074

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Guma M, Angulo A, Vilches C, Gomez-Lozano N, Malats N, Lopez-Botet M (2004) Imprint of human cytomegalovirus infection on the NK cell receptor repertoire. Blood 104(12):3664–3671. doi:10.1182/blood-2004-05-2058 2004-05-2058 [pii]

  • Guma M, Budt M, Saez A, Brckalo T, Hengel H, Angulo A et al (2006) Expansion of CD94/NKG2C+ NK cells in response to human cytomegalovirus-infected fibroblasts. Blood 107(9):3624–3631. doi:2005-09-3682 [pii] 10.1182/blood-2005-09-3682

  • Handgretinger R (2012) New approaches to graft engineering for haploidentical bone marrow transplantation. Semin Oncol 39(6):664–673. doi:10.1053/j.seminoncol.2012.09.007

    Article  CAS  PubMed  Google Scholar 

  • Heatley SL, Pietra G, Lin J, Widjaja JM, Harpur CM, Lester S et al (2013) Polymorphism in human cytomegalovirus UL40 impacts on recognition of human leukocyte antigen-E (HLA-E) by natural killer cells. J Biol Chem 288(12):8679–8690. doi:M112.409672 [pii] 10.1074/jbc.M112.409672

  • Jiang H, Zhang W, Shang P, Zhang H, Fu W, Ye F et al (2014) Transfection of chimeric anti-CD138 gene enhances natural killer cell activation and killing of multiple myeloma cells. Mol Oncol 8(2):297–310. doi:10.1016/j.molonc.2013.12.001

    Article  CAS  PubMed  Google Scholar 

  • Kheav VD, Busson M, Scieux C, Peffault de Latour R, Maki G, Haas P et al (2014) Favorable impact of natural killer cell reconstitution on chronic graft-versus-host disease and cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation. Haematologica 99(12):1860–1867. doi:10.3324/haematol.2014.108407

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kohrt HE, Thielens A, Marabelle A, Sagiv-Barfi I, Sola C, Chanuc F et al (2014) Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells as monotherapy and in combination with anti-CD20 antibodies. Blood 123(5):678–686. doi:10.1182/blood-2013-08-519199

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kuijpers TW, Baars PA, Dantin C, van den Burg M, van Lier RA, Roosnek E (2008) Human NK cells can control CMV infection in the absence of T cells. Blood 112(3):914–915. doi:112/3/914 [pii] 10.1182/blood-2008-05-157354

  • Lee J, Zhang T, Hwang I, Kim A, Nitschke L, Kim M et al (2015) Epigenetic Modification and Antibody-Dependent Expansion of Memory-like NK Cells in Human Cytomegalovirus-Infected Individuals. Immunity 42(3):431–442. doi:10.1016/j.immuni.2015.02.013

    Article  CAS  PubMed  Google Scholar 

  • Locatelli F, Merli P, Rutella S (2013a) At the Bedside: innate immunity as an immunotherapy tool for hematological malignancies. J Leukoc Biol 94(6):1141–1157. doi:10.1189/jlb.0613343

    Article  PubMed  Google Scholar 

  • Locatelli F, Pende D, Mingari MC, Bertaina A, Falco M, Moretta A et al (2013b) Cellular and molecular basis of haploidentical hematopoietic stem cell transplantation in the successful treatment of high-risk leukemias: role of alloreactive NK cells. Front Immunol 4:15. doi:10.3389/fimmu.2013.00015

    Article  PubMed Central  PubMed  Google Scholar 

  • Lopez-Botet M, Muntasell A, Vilches C (2014) The CD94/NKG2C+ NK-cell subset on the edge of innate and adaptive immunity to human cytomegalovirus infection. Semin Immunol 26(2):145–151. doi:10.1016/j.smim.2014.03.002

    Article  CAS  PubMed  Google Scholar 

  • Luetke-Eversloh M, Hammer Q, Durek P, Nordstrom K, Gasparoni G, Pink M et al (2014) Human cytomegalovirus drives epigenetic imprinting of the IFNG locus in NKG2Chi natural killer cells. PLoS Pathog 10(10):e1004441. doi:10.1371/journal.ppat.1004441

    Article  PubMed Central  PubMed  Google Scholar 

  • Mancusi A, Ruggeri L, Urbani E, Pierini A, Massei MS, Carotti A et al (2015) Haploidentical hematopoietic transplantation from KIR ligand-mismatched donors with activating KIRs reduces nonrelapse mortality. Blood 125(20):3173–3182. doi:10.1182/blood-2014-09-599993

    Article  CAS  PubMed  Google Scholar 

  • Manjappa S, Bhamidipati PK, Stokerl-Goldstein KE, DiPersio JF, Uy GL, Westervelt P et al (2014) Protective effect of cytomegalovirus reactivation on relapse after allogeneic hematopoietic cell transplantation in acute myeloid leukemia patients is influenced by conditioning regimen. Biol Blood Marrow Transpl 20(1):46–52. doi:10.1016/j.bbmt.2013.10.003

    Article  CAS  Google Scholar 

  • Marcus A, Raulet DH (2013) Evidence for natural killer cell memory. Current biology: CB. 23(17):R817–R820. doi:10.1016/j.cub.2013.07.015

    Article  CAS  PubMed  Google Scholar 

  • Mavilio D, Lombardo G, Benjamin J, Kim D, Follman D, Marcenaro E et al (2005) Characterization of CD56−/CD16+ natural killer (NK) cells: a highly dysfunctional NK subset expanded in HIV-infected viremic individuals. Proc Natl Acad Sci U S A. 102(8):2886–2891. doi:0409872102 [pii] 10.1073/pnas.0409872102

  • Montaldo E, Del Zotto G, Della Chiesa M, Mingari MC, Moretta A, De Maria A et al (2013) Human NK cell receptors/markers: a tool to analyze NK cell development, subsets and function. Cytometry Part A J Int Soc Anal Cytol 83(8):702–713. doi:10.1002/cyto.a.22302

    Article  Google Scholar 

  • Moretta A, Bottino C, Vitale M, Pende D, Biassoni R, Mingari MC et al (1996) Receptors for HLA class-I molecules in human natural killer cells. Annu Rev Immunol 14:619–648. doi:10.1146/annurev.immunol.14.1.619

    Article  CAS  PubMed  Google Scholar 

  • Moretta A, Bottino C, Vitale M, Pende D, Cantoni C, Mingari MC et al (2001) Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol 19:197–223. doi:19/1/197 [pii] 10.1146/annurev.immunol.19.1.197

  • Moretta L, Bottino C, Pende D, Mingari MC, Biassoni R, Moretta A (2002) Human natural killer cells: their origin, receptors and function. Eur J Immunol 32(5):1205–1211. doi:10.1002/1521-4141(200205)32:5<1205:AID-IMMU1205>3.0.CO;2-Y

    Article  CAS  PubMed  Google Scholar 

  • Moretta L, Bottino C, Pende D, Vitale M, Mingari MC, Moretta A (2004) Different checkpoints in human NK-cell activation. Trends Immunol 25(12):670–676. doi:10.1016/j.it.2004.09.008

    Article  CAS  PubMed  Google Scholar 

  • Muntasell A, Vilches C, Angulo A, Lopez-Botet M (2013) Adaptive reconfiguration of the human NK-cell compartment in response to cytomegalovirus: a different perspective of the host-pathogen interaction. Eur J Immunol 43(5):1133–1141. doi:10.1002/eji.201243117

    Article  CAS  PubMed  Google Scholar 

  • Norell H, Moretta A, Silva-Santos B, Moretta L (2013) At the Bench: Preclinical rationale for exploiting NK cells and gammadelta T lymphocytes for the treatment of high-risk leukemias. J Leukoc Biol 94(6):1123–1139. doi:10.1189/jlb.0613312

    Article  PubMed  Google Scholar 

  • Oevermann L, Michaelis SU, Mezger M, Lang P, Toporski J, Bertaina A et al (2014) KIR B haplotype donors confer a reduced risk for relapse after haploidentical transplantation in children with ALL. Blood 124(17):2744–2747. doi:10.1182/blood-2014-03-565069

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pende D, Marcenaro S, Falco M, Martini S, Bernardo ME, Montagna D et al (2009) 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. Blood 113(13):3119–3129. doi:10.1182/blood-2008-06-164103

    Article  CAS  PubMed  Google Scholar 

  • Reisner Y, Kapoor N, Kirkpatrick D, Pollack MS, Cunningham-Rundles S, Dupont B et al (1983) Transplantation for severe combined immunodeficiency with HLA-A, B, D, DR incompatible parental marrow cells fractionated by soybean agglutinin and sheep red blood cells. Blood 61(2):341–348

    CAS  PubMed  Google Scholar 

  • Rolle A, Pollmann J, Ewen EM, Le VT, Halenius A, Hengel H et al (2014) IL-12-producing monocytes and HLA-E control CMV-driven NKG2C+ NK cell expansion. J Clin Investig 124(12):5305–5316. doi:10.1172/JCI77440

    Article  PubMed Central  PubMed  Google Scholar 

  • Romagne F, Andre P, Spee P, Zahn S, Anfossi N, Gauthier L et al (2009) Preclinical characterization of 1-7F9, a novel human anti-KIR receptor therapeutic antibody that augments natural killer-mediated killing of tumor cells. Blood 114(13):2667–2677. doi:10.1182/blood-2009-02-206532

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A et al (2002) Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 295(5562):2097–2100. doi:10.1126/science.1068440

    Article  CAS  PubMed  Google Scholar 

  • Schlums H, Cichocki F, Tesi B, Theorell J, Beziat V, Holmes TD et al (2015) Cytomegalovirus infection drives adaptive epigenetic diversification of NK cells with altered signaling and effector function. Immunity 42(3):443–456. doi:10.1016/j.immuni.2015.02.008

    Article  CAS  PubMed  Google Scholar 

  • Shi FD, Ljunggren HG, La Cava A, Van Kaer L (2011) Organ-specific features of natural killer cells. Nat Rev Immunol 11(10):658–671. doi:10.1038/nri3065

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Stern M, Elsasser H, Honger G, Steiger J, Schaub S, Hess C (2008) The number of activating KIR genes inversely correlates with the rate of CMV infection/reactivation in kidney transplant recipients. Am J Transpl 8(6):1312–1317. doi:AJT2242 [pii] 10.1111/j.1600-6143.2008.02242.x

  • Stern M, Ruggeri L, Mancusi A, Bernardo ME, de Angelis C, Bucher C et al (2008) Survival after T cell-depleted haploidentical stem cell transplantation is improved using the mother as donor. Blood 112(7):2990–2995. doi:10.1182/blood-2008-01-135285

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Stern M, Hadaya K, Honger G, Martin PY, Steiger J, Hess C et al (2011) Telomeric rather than centromeric activating KIR genes protect from cytomegalovirus infection after kidney transplantation. Am J Transpl 11(6):1302–1307. doi:10.1111/j.1600-6143.2011.03516.x

    Article  CAS  Google Scholar 

  • Sun JC, Lanier LL (2011) NK cell development, homeostasis and function: parallels with CD8(+) T cells. Nat Rev Immunol 11(10):645–657. doi:10.1038/nri3044

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sun JC, Beilke JN, Lanier LL (2009) Adaptive immune features of natural killer cells. Nature 457(7229):557–561. doi:nature07665 [pii] 10.1038/nature07665

  • Symons HJ, Leffell MS, Rossiter ND, Zahurak M, Jones RJ, Fuchs EJ (2010) Improved survival with inhibitory killer immunoglobulin receptor (KIR) gene mismatches and KIR haplotype B donors after nonmyeloablative, HLA-haploidentical bone marrow transplantation. Biol Blood Marrow Transpl 16(4):533–542. doi:10.1016/j.bbmt.2009.11.022

    Article  Google Scholar 

  • Topfer K, Cartellieri M, Michen S, Wiedemuth R, Muller N, Lindemann D et al (2015) DAP12-Based Activating Chimeric Antigen Receptor for NK Cell Tumor Immunotherapy. J Immunol 194(7):3201–3212. doi:10.4049/jimmunol.1400330

    Article  PubMed  Google Scholar 

  • Tortorella D, Gewurz BE, Furman MH, Schust DJ, Ploegh HL (2000) Viral subversion of the immune system. Annu Rev Immunol 18:861–926. doi:18/1/861 [pii] 10.1146/annurev.immunol.18.1.861

  • Venstrom JM, Pittari G, Gooley TA, Chewning JH, Spellman S, Haagenson M et al (2012) HLA-C-dependent prevention of leukemia relapse by donor activating KIR2DS1. New Engl J Med 367(9):805–816. doi:10.1056/NEJMoa1200503

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wiernik A, Foley B, Zhang B, Verneris MR, Warlick E, Gleason MK et al (2013) Targeting natural killer cells to acute myeloid leukemia in vitro with a CD16 x 33 bispecific killer cell engager and ADAM17 inhibition. Clin Cancer Res Off J Amer Assoc Cancer Res 19(14):3844–3855. doi:10.1158/1078-0432.CCR-13-0505

    Article  CAS  Google Scholar 

  • Williams MA, Bevan MJ (2007) Effector and memory CTL differentiation. Annu Rev Immunol 25:171–192. doi:10.1146/annurev.immunol.25.022106.141548

    Article  CAS  PubMed  Google Scholar 

  • Wu Z, Sinzger C, Frascaroli G, Reichel J, Bayer C, Wang L et al (2013) Human cytomegalovirus-induced NKG2C(hi) CD57(hi) natural killer cells are effectors dependent on humoral antiviral immunity. J Virol 87(13):7717–7725. doi:JVI.01096-13 [pii] 10.1128/JVI.01096-13

  • Zaia JA, Sun JY, Gallez-Hawkins GM, Thao L, Oki A, Lacey SF et al (2009) The effect of single and combined activating killer immunoglobulin-like receptor genotypes on cytomegalovirus infection and immunity after hematopoietic cell transplantation. Biol Blood Marrow Transpl 15(3):315–325. doi:S1083-8791(08)00580-6 [pii] 10.1016/j.bbmt.2008.11.030

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Acknowledgments

Supported by grants awarded by Associazione Italiana Ricerca sul Cancro: IG projects, n. 15704 (A.M) and n. 15283 (L.M.) and Special Project 5x1000 n. 9962 (A.M., L.M., F.L.) and by Cordon de Vie (F.L.).

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Authors and Affiliations

  1. Dipartimento di Medicina Sperimentale, Sezione Istologia and Centro di Eccellenza per la Ricerca Biomedica, Università di Genova, Via G.B. Marsano 10, 16132, Genoa, Italy

    Mariella Della Chiesa, Letizia Muccio & Alessandro Moretta

  2. IRCCS Istituto Giannina Gaslini, Genoa, Italy

    Lorenzo Moretta

  3. Department of Pediatric Hematology/Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy

    Alice Bertaina & Franco Locatelli

  4. Department of Medicine, University of Verona and Ospedale Sacro Cuore Negrar (VR), Verona, Italy

    Francesca Moretta

  5. Department of Pediatrics, University of Pavia, Pavia, Italy

    Franco Locatelli

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  1. Mariella Della Chiesa
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  2. Lorenzo Moretta
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  6. Franco Locatelli
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  7. Alessandro Moretta
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Corresponding author

Correspondence to Mariella Della Chiesa .

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Editors and Affiliations

  1. Assistance Publique des Hôpitaux de Marseille, Marseille 05, France and Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université - INSERM - CNRS, Marseille 09, France

    Eric Vivier

  2. INSERM U 668, Pasteur Institute, Paris, Paris, France

    James Di Santo

  3. University of Genoa, Genova, Italy

    Alessandro Moretta

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© 2015 Springer International Publishing Switzerland

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Della Chiesa, M. et al. (2015). Haploidentical Haematopoietic Stem Cell Transplantation: Role of NK Cells and Effect of Cytomegalovirus Infections . In: Vivier, E., Di Santo, J., Moretta, A. (eds) Natural Killer Cells. Current Topics in Microbiology and Immunology, vol 395. Springer, Cham. https://doi.org/10.1007/82_2015_450

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