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

  • Mariella Della Chiesa
  • Lorenzo Moretta
  • Letizia Muccio
  • Alice Bertaina
  • Francesca Moretta
  • Franco Locatelli
  • Alessandro Moretta
Part of the Current Topics in Microbiology and Immunology book series (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.

Keywords

Natural Killer Cell Leukemia Relapse Natural Killer Cell Subset Umbilical Cord Blood Transplantation Peripheral Blood Natural Killer Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

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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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Mariella Della Chiesa
    • 1
  • Lorenzo Moretta
    • 2
  • Letizia Muccio
    • 1
  • Alice Bertaina
    • 3
  • Francesca Moretta
    • 4
  • Franco Locatelli
    • 3
    • 5
  • Alessandro Moretta
    • 1
  1. 1.Dipartimento di Medicina Sperimentale, Sezione Istologia and Centro di Eccellenza per la Ricerca BiomedicaUniversità di GenovaGenoaItaly
  2. 2.IRCCS Istituto Giannina GasliniGenoaItaly
  3. 3.Department of Pediatric Hematology/OncologyIRCCS Ospedale Pediatrico Bambino GesùRomeItaly
  4. 4.Department of MedicineUniversity of Verona and Ospedale Sacro Cuore Negrar (VR)VeronaItaly
  5. 5.Department of PediatricsUniversity of PaviaPaviaItaly

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