PMID- 28807569
OWN - NLM
STAT- MEDLINE
DCOM- 20180618
LR  - 20240215
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 25
IP  - 10
DP  - 2017 Oct 4
TI  - IL-10-Engineered Human CD4(+) Tr1 Cells Eliminate Myeloid Leukemia in an HLA 
      Class I-Dependent Mechanism.
PG  - 2254-2269
LID - S1525-0016(17)30314-3 [pii]
LID - 10.1016/j.ymthe.2017.06.029 [doi]
AB  - T regulatory cells (Tregs) play a key role in modulating T cell responses. 
      Clinical trials showed that Tregs modulate graft-versus-host disease (GvHD) after 
      allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, their 
      ability to mediate anti-leukemic activity (graft-versus-leukemia [GvL]) is 
      largely unknown. Enforced interleukin-10 (IL-10) expression converts human CD4(+) 
      T cells into T regulatory type 1 (Tr1)-like (CD4(IL-10)) cells that suppress 
      effector T cells in vitro and xenoGvHD in humanized mouse models. In the present 
      study, we show that CD4(IL-10) cells mediate anti-leukemic effects in vitro and 
      in vivo in a human leukocyte antigen (HLA) class I-dependent but 
      antigen-independent manner. The cytotoxicity mediated by CD4(IL-10) cells is 
      granzyme B (GzB) dependent, is specific for CD13(+) target cells, and requires 
      CD54 and CD112 expression on primary leukemic target blasts. CD4(IL-10) cells 
      adoptively transferred in humanized mouse models directly mediate anti-tumor and 
      anti-leukemic effects. In addition, when co-transferred with peripheral blood 
      mononuclear cells (PBMCs), CD4(IL-10) cells contribute to the GvL activity but 
      suppress xenoGvHD mediated by the PBMCs. These findings provide for the first 
      time a strong rationale for CD4(IL-10) cell immunotherapy to prevent GvHD and 
      promote GvL in allo-HSCT for myeloid malignancies.
CI  - Copyright (c) 2017. Published by Elsevier Inc.
FAU - Locafaro, Grazia
AU  - Locafaro G
AD  - San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele 
      Scientific Institute, Milan 20132, Italy.
FAU - Andolfi, Grazia
AU  - Andolfi G
AD  - San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele 
      Scientific Institute, Milan 20132, Italy.
FAU - Russo, Fabio
AU  - Russo F
AD  - San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele 
      Scientific Institute, Milan 20132, Italy.
FAU - Cesana, Luca
AU  - Cesana L
AD  - San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele 
      Scientific Institute, Milan 20132, Italy.
FAU - Spinelli, Antonello
AU  - Spinelli A
AD  - Experimental Imaging Centre, IRCCS San Raffaele Scientific Institute, Milan 
      20132, Italy.
FAU - Camisa, Barbara
AU  - Camisa B
AD  - Innovative Immunotherapies Unit, Division of Immunology, Transplantation and 
      Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy.
FAU - Ciceri, Fabio
AU  - Ciceri F
AD  - Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific 
      Institute, Milan 20132, Italy.
FAU - Lombardo, Angelo
AU  - Lombardo A
AD  - San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele 
      Scientific Institute, Milan 20132, Italy; Vita Salute San Raffaele University, 
      Milan 20132, Italy.
FAU - Bondanza, Attilio
AU  - Bondanza A
AD  - Experimental Imaging Centre, IRCCS San Raffaele Scientific Institute, Milan 
      20132, Italy.
FAU - Roncarolo, Maria Grazia
AU  - Roncarolo MG
AD  - San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele 
      Scientific Institute, Milan 20132, Italy; Division of Stem Cell Transplantation 
      and Regenerative Medicine, Department of Pediatrics, ISCBRM, Stanford School of 
      Medicine, Stanford, CA 94305, USA. Electronic address: mg1@stanford.edu.
FAU - Gregori, Silvia
AU  - Gregori S
AD  - San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele 
      Scientific Institute, Milan 20132, Italy. Electronic address: 
      gregori.silvia@hsr.it.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170705
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
EIN - Mol Ther. 2024 Mar 6;32(3):853-854. PMID: 38359840
MH  - CD4-Positive T-Lymphocytes
MH  - Humans
MH  - Immunotherapy
MH  - Interleukin-10/*metabolism
MH  - Leukemia, Myeloid/immunology/metabolism/*therapy
MH  - Leukocytes, Mononuclear/*metabolism
MH  - Models, Biological
MH  - T-Lymphocytes, Regulatory/*metabolism
PMC - PMC5628869
OTO - NOTNLM
OT  - gene transfer
OT  - immunotherapy
OT  - tolerance
EDAT- 2017/08/16 06:00
MHDA- 2018/06/19 06:00
PMCR- 2018/10/04
CRDT- 2017/08/16 06:00
PHST- 2017/01/27 00:00 [received]
PHST- 2017/06/28 00:00 [revised]
PHST- 2017/06/29 00:00 [accepted]
PHST- 2017/08/16 06:00 [pubmed]
PHST- 2018/06/19 06:00 [medline]
PHST- 2017/08/16 06:00 [entrez]
PHST- 2018/10/04 00:00 [pmc-release]
AID - S1525-0016(17)30314-3 [pii]
AID - 10.1016/j.ymthe.2017.06.029 [doi]
PST - ppublish
SO  - Mol Ther. 2017 Oct 4;25(10):2254-2269. doi: 10.1016/j.ymthe.2017.06.029. Epub 
      2017 Jul 5.