PMID- 28405496
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210112
IS  - 2162-4011 (Print)
IS  - 2162-402X (Electronic)
IS  - 2162-4011 (Linking)
VI  - 6
IP  - 3
DP  - 2017
TI  - IL-12, IL-15, and IL-18 pre-activated NK cells target resistant T cell acute 
      lymphoblastic leukemia and delay leukemia development in vivo.
PG  - e1274478
LID - 10.1080/2162402X.2016.1274478 [doi]
LID - e1274478
AB  - NK cells have shown promise in therapy of hematological cancers, in particular 
      against acute myeloid leukemia. In contrast, the more NK cell-resistant acute 
      lymphoblastic leukemia (ALL) is difficult to treat with NK-cell-based therapies, 
      and we hypothesized that pre-activation of NK cells could overcome this 
      resistance. We show in pediatric and adult patients with T-cell ALL (T-ALL) 
      perturbed NK cell effector functions at diagnosis. Using an in vivo rat model for 
      T-ALL, Roser leukemia (RL), suppressed NK cell effector functions were observed. 
      NK cells from T-ALL patients had reduced expression of the activating receptors 
      NKp46 and DNAM-1, but not NKG2D. In contrast to T-ALL patients, NKG2D but not 
      NKp46 was downregulated on NK cells during rat RL. Decreased frequencies of 
      terminally differentiated NKG2A(+)CD57(-)CD56(dim) NK cells in human T-ALL was 
      paralleled in the rat by reduced frequencies of bone marrow NK cells expressing 
      the maturation marker CD11b, possibly indicating impairment of differentiation 
      during leukemia. RL was highly resistant to autologous NK cells, but this 
      resistance was overcome upon pre-activation of NK cells with IL-12, IL-15, and 
      IL-18, with concomitant upregulation of activation markers and activating 
      receptors. Importantly, adoptive transfers of IL-12, IL-15, and IL-18 
      pre-activated NK cells significantly slowed progression of RL in vivo. The data 
      thus shows that T-ALL blasts normally resistant to NK cells may be targeted by 
      cytokine pre-activated autologous NK cells, and this approach could have 
      potential implications for immunotherapeutic protocols using NK cells to more 
      efficiently target leukemia.
FAU - Boieri, Margherita
AU  - Boieri M
AD  - Department of Molecular Medicine, Institute of Basic Medical Sciences, University 
      of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital, Oslo, 
      Norway.
FAU - Ulvmoen, Aina
AU  - Ulvmoen A
AD  - Department of Immunology, Oslo University Hospital , Oslo, Norway.
FAU - Sudworth, Amanda
AU  - Sudworth A
AD  - Department of Immunology, Oslo University Hospital , Oslo, Norway.
FAU - Lendrem, Clare
AU  - Lendrem C
AD  - Institute of Cellular Medicine, Medical School, Newcastle University , 
      Newcastle-upon-Tyne, UK.
FAU - Collin, Matthew
AU  - Collin M
AD  - Institute of Cellular Medicine, Medical School, Newcastle University , 
      Newcastle-upon-Tyne, UK.
FAU - Dickinson, Anne M
AU  - Dickinson AM
AD  - Institute of Cellular Medicine, Medical School, Newcastle University , 
      Newcastle-upon-Tyne, UK.
FAU - Kveberg, Lise
AU  - Kveberg L
AD  - Department of Immunology, Institute of Clinical Medicine, University of Oslo , 
      Oslo, Norway.
FAU - Inngjerdingen, Marit
AU  - Inngjerdingen M
AD  - Department of Immunology, Oslo University Hospital , Oslo, Norway.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170117
PL  - United States
TA  - Oncoimmunology
JT  - Oncoimmunology
JID - 101570526
PMC - PMC5384344
OTO - NOTNLM
OT  - DNAM-1
OT  - IL-12
OT  - IL-15
OT  - IL-18
OT  - NK cells
OT  - T-ALL
EDAT- 2017/04/14 06:00
MHDA- 2017/04/14 06:01
PMCR- 2018/01/17
CRDT- 2017/04/14 06:00
PHST- 2016/10/17 00:00 [received]
PHST- 2016/12/15 00:00 [revised]
PHST- 2016/12/15 00:00 [accepted]
PHST- 2017/04/14 06:00 [entrez]
PHST- 2017/04/14 06:00 [pubmed]
PHST- 2017/04/14 06:01 [medline]
PHST- 2018/01/17 00:00 [pmc-release]
AID - 1274478 [pii]
AID - 10.1080/2162402X.2016.1274478 [doi]
PST - epublish
SO  - Oncoimmunology. 2017 Jan 17;6(3):e1274478. doi: 10.1080/2162402X.2016.1274478. 
      eCollection 2017.