Exploitation of alloreactive NK cells in adoptive immunotherapy of cancer

Curr Opin Immunol. 2005 Apr;17(2):211-7. doi: 10.1016/j.coi.2005.01.007.


NK cells are primed to kill by several activating receptors. Killing of autologous cells is prevented as NK cells co-express inhibitory receptors for self-MHC class I molecules. Human NK cells discriminate between different allelic forms of MHC molecules via killer cell immunoglobulin-like receptors (KIRs), which are clonally distributed, and each cell in the repertoire bears at least one receptor that is specific for self-MHC class I molecules. Consequently, when faced with mismatched allogeneic targets, NK cells in the repertoire will sense the missing expression of self-MHC class I alleles and will mediate alloreactions. Recent studies in murine transplant models and data from mismatched haematopoietic transplant trials demonstrate MHC class I mismatches, which generate an alloreactive NK-cell response in the graft-versus-host direction, eradicate leukaemia, improve engraftment and protect against T-cell-mediated graft-versus-host disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Bone Marrow Transplantation
  • Humans
  • Immunotherapy, Adoptive*
  • Isoantibodies / immunology
  • Isoantigens / immunology
  • Killer Cells, Natural / immunology*
  • Neoplasms / immunology*
  • Neoplasms / therapy*


  • Isoantibodies
  • Isoantigens