PMID- 31703320
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2077-0383 (Print)
IS  - 2077-0383 (Electronic)
IS  - 2077-0383 (Linking)
VI  - 8
IP  - 11
DP  - 2019 Nov 7
TI  - NK Cell Reconstitution in Paediatric Leukemic Patients after T-Cell-Depleted 
      HLA-Haploidentical Haematopoietic Stem Cell Transplantation Followed by the 
      Reinfusion of iCasp9-Modified Donor T Cells.
LID - 10.3390/jcm8111904 [doi]
LID - 1904
AB  - T-cell-depleted (TCD) human leukocyte antigen (HLA) haploidentical (haplo) 
      hematopoietic stem cell transplantation (HSCT) (TCD-haplo-HSCT) has had a huge 
      impact on the treatment of many haematological diseases. The adoptive transfer of 
      a titrated number of T cells genetically modified with a gene suicide can improve 
      immune reconstitution and represents an interesting strategy to enhance the 
      success of haplo-HSCT. Natural killer (NK) cells are the first donor-derived 
      lymphocyte population to reconstitute following transplantation, and play a 
      pivotal role in mediating graft-versus-leukaemia (GvL). We recently described a 
      CD56(low)CD16(low) NK cell subset that mediates both cytotoxic activity and 
      cytokine production. Given the multifunctional properties of this subset, we 
      studied its functional recovery in a cohort of children given alpha/betaT-cell-depleted 
      haplo-HSCT followed by the infusion of a titrated number of iCasp-9-modified T 
      cells (iCasp-9 HSCT). The data obtained indicate that multifunctional 
      CD56(low)CD16(low) NK cell frequency is similar to that of healthy donors (HD) at 
      all time points analysed, showing enrichment in the bone marrow (BM). 
      Interestingly, with regard to functional acquisition, we identified two groups of 
      patients, namely those whose NK cells did (responder) or did not (non responder) 
      degranulate or produce cytokines. Moreover, in patients analysed for both 
      functions, we observed that the acquisition of degranulation capacity was not 
      associated with the ability to produce interferon-gamma (IFN-gamma Intriguingly, we 
      found a higher BM and peripheral blood (PB) frequency of iCas9 donor T cells only 
      in patients characterized by the ability of CD56(low)CD16(low) NK cells to 
      degranulate. Collectively, these findings suggest that donor iCasp9-T lymphocytes 
      do not have a significant influence on NK cell reconstitution, even if they may 
      positively affect the acquisition of target-induced degranulation of 
      CD56(low)CD16(low) NK cells in the T-cell-depleted haplo-HSC transplanted 
      patients.
FAU - Stabile, Helena
AU  - Stabile H
AD  - Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, 
      Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur 
      Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy.
FAU - Nisti, Paolo
AU  - Nisti P
AD  - Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, 
      Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur 
      Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy.
FAU - Fionda, Cinzia
AU  - Fionda C
AD  - Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, 
      Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur 
      Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy.
FAU - Pagliara, Daria
AU  - Pagliara D
AD  - Department of Pediatric Hematology/Oncology, Istituto di Ricovero e Cura a 
      Carattere Scientifico (IRCCS) Ospedale Pediatrico Bambino Gesu, 00165 Rome, 
      Italy.
FAU - Gaspari, Stefania
AU  - Gaspari S
AD  - Department of Pediatric Hematology/Oncology, Istituto di Ricovero e Cura a 
      Carattere Scientifico (IRCCS) Ospedale Pediatrico Bambino Gesu, 00165 Rome, 
      Italy.
FAU - Locatelli, Franco
AU  - Locatelli F
AD  - Department of Pediatric Hematology/Oncology, Istituto di Ricovero e Cura a 
      Carattere Scientifico (IRCCS) Ospedale Pediatrico Bambino Gesu, 00165 Rome, 
      Italy.
AD  - Department of Pediatrics, Sapienza, University of Rome, 00161 Rome, Italy.
FAU - Santoni, Angela
AU  - Santoni A
AD  - Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, 
      Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur 
      Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy.
FAU - Gismondi, Angela
AU  - Gismondi A
AD  - Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, 
      Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur 
      Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy.
LA  - eng
GR  - code. 9962/Associazione Italiana per la Ricerca sul Cancro/
GR  - code. 20174T7NXL_003/Ministero dell'Istruzione, dell'Universita e della Ricerca/
PT  - Journal Article
DEP - 20191107
PL  - Switzerland
TA  - J Clin Med
JT  - Journal of clinical medicine
JID - 101606588
PMC - PMC6912839
OTO - NOTNLM
OT  - Bone marrow transplantation
OT  - NK cell subsets
OT  - haematological disease
OT  - iCasp-9 HSCT
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could represent a potential conflict 
      of interest.
EDAT- 2019/11/11 06:00
MHDA- 2019/11/11 06:01
PMCR- 2019/11/07
CRDT- 2019/11/10 06:00
PHST- 2019/09/19 00:00 [received]
PHST- 2019/10/29 00:00 [revised]
PHST- 2019/11/05 00:00 [accepted]
PHST- 2019/11/10 06:00 [entrez]
PHST- 2019/11/11 06:00 [pubmed]
PHST- 2019/11/11 06:01 [medline]
PHST- 2019/11/07 00:00 [pmc-release]
AID - jcm8111904 [pii]
AID - jcm-08-01904 [pii]
AID - 10.3390/jcm8111904 [doi]
PST - epublish
SO  - J Clin Med. 2019 Nov 7;8(11):1904. doi: 10.3390/jcm8111904.