PMID- 22954728
OWN - NLM
STAT- MEDLINE
DCOM- 20130509
LR  - 20210103
IS  - 1531-7048 (Electronic)
IS  - 1065-6251 (Linking)
VI  - 19
IP  - 6
DP  - 2012 Nov
TI  - Natural killer cell alloreactivity 10 years later.
PG  - 421-6
LID - 10.1097/MOH.0b013e3283590395 [doi]
AB  - PURPOSE OF REVIEW: This article reviews the impact of natural killer (NK) cell 
      alloreactivity on hematopoietic cell transplantation since it was first observed 
      in haploidentical transplant recipients 10 years ago. RECENT FINDINGS: Research 
      has established 'missing self-recognition' as the mechanism underlying NK 
      cell-mediated graft-versus-leukemia effects in T-cell-depleted haploidentical 
      hematopoietic cell transplantation and has clarified optimal transplantation 
      protocols to harness NK cell alloreactivity. SUMMARY: In the past decade, 
      clinical studies have shown that the benefits of donor-versus-recipient NK cell 
      alloreactivity in haploidentical transplantation are triggered by specific human 
      leukocyte antigen (HLA) class I mismatches. Donor HLA is crucial for driving NK 
      cell education so that reconstituting NK cells mature as donor-tolerant and 
      recipient-alloreactive. Transplantation of large doses of extensively 
      T-cell-depleted hematopoietic grafts with no posttransplant immune suppression 
      was found to be essential for development of NK cell alloreactivity. Clinical 
      trials demonstrated that donor-versus-recipient NK cell alloreactivity is a key 
      therapeutic element in haploidentical transplants for acute myeloblastic leukemia 
      in adults and acute lymphoblastic leukemia in children. Moreover, in pilot 
      studies, mature haploidentical NK cells were transiently transferred into 
      lymphoablated patients with acute leukemia in remission. The results showed NK 
      cell therapy may be a promising strategy for consolidating leukemia remission. In 
      line with the notion that NK cell function is regulated by a balance between 
      activating and inhibitory receptors, in the matched transplant setting, 
      transplantation from donors possessing certain activating NK receptors 
      (activating killer cell immunoglobulin-like receptors) appeared to protect from 
      relapse and improved survival.
FAU - Velardi, Andrea
AU  - Velardi A
AD  - Division of Hematology and Clinical Immunology, Department of Clinical and 
      Experimental Medicine, University of Perugia, Perugia, Italy. velardi@unipg.it
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Curr Opin Hematol
JT  - Current opinion in hematology
JID - 9430802
SB  - IM
MH  - Animals
MH  - Hematopoietic Stem Cell Transplantation/*methods
MH  - Humans
MH  - Killer Cells, Natural/*immunology
MH  - Transplantation Immunology
EDAT- 2012/09/08 06:00
MHDA- 2013/05/10 06:00
CRDT- 2012/09/08 06:00
PHST- 2012/09/08 06:00 [entrez]
PHST- 2012/09/08 06:00 [pubmed]
PHST- 2013/05/10 06:00 [medline]
AID - 10.1097/MOH.0b013e3283590395 [doi]
PST - ppublish
SO  - Curr Opin Hematol. 2012 Nov;19(6):421-6. doi: 10.1097/MOH.0b013e3283590395.