Natural killer cells in the treatment of high-risk acute leukaemia

Semin Immunol. 2014 Apr;26(2):173-9. doi: 10.1016/j.smim.2014.02.004. Epub 2014 Mar 5.


Several studies have shown that in patients with acute leukaemia given allogeneic haematopoietic stem cell transplantation (allo-HSCT) large part of the therapeutic effect lies on the anti-tumour effect displayed by cells of both adaptive and innate immunity. This evidence has also opened new scenarios for the treatment of patients with other haematological malignancies/solid tumours. In particular, donor-derived natural killer (NK) cells play a crucial role in the eradication of cancer cells in patients given an allograft from an HLA-haploidentical relative, especially when there is a killer inhibitory-receptor (KIR)-KIR ligand mismatched in the donor-recipient direction. Alloreactive donor-derived NK cells have been also demonstrated to kill recipient antigen-presenting cells and cytotoxic T lymphocytes, thus preventing graft-versus-host disease (GvHD) and graft rejection and to largely contribute to the defence against cytomegalovirus infection in the early post-transplant period. Several clinical studies have recently focused also on the influence of NK-cell activating receptors on the outcome of allo-HSCT recipients; in particular, B/x haplotype donors offer clinical advantages compared with A/A donors, even when the donor is an HLA-identical volunteer. Altogether, these data have provided the rationale for implementing phase I/II clinical trials based on adoptive infusion of either selected or ex vivo activated NK cells from an HLA-mismatched donor. This review summarizes the biological and clinical data on the role played by NK cells in patients with high-risk acute leukaemia, focusing also on the still unsolved issues and the future perspectives related to the approaches of adoptive NK cell therapy.

Keywords: Adoptive immunotherapy with NK cells; Allogeneic hematopoietic stem cell transplantation; Inhibitory and activating NK-cell receptors; Innate immunity; KIR–KIR ligand mismatched; Redirection of NK-cell cytotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acute Disease
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunotherapy, Adoptive
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Killer Cells, Natural / transplantation*
  • Leukemia / immunology*
  • Leukemia / therapy*
  • Tissue Donors
  • Transplantation, Homologous