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JCR 2016
جستجوی مقالات
چهارشنبه 26 آذر 1404
Cell Journal
، جلد ۲۵، شماره ۲، صفحات ۹۲-۱۰۱
عنوان فارسی
چکیده فارسی مقاله
کلیدواژههای فارسی مقاله
عنوان انگلیسی
Hsp70, in Combination with IL-15 and PD-1 Blocker, Interferes with The Induction of Cytotoxic NK Cells in Relapsed Acute Myeloid Leukemia Patients
چکیده انگلیسی مقاله
Objective:
Natural killer (NK) cells are critical immune cells for acute myeloid leukemia (AML) targeting. However,
little is known about the relationship between using checkpoint inhibitors and heat shock protein 70 (Hsp70) as NK cell
activators to control AML. Therefore, the study aims to find the best formulation of Hsp70, human PD-1 (Programmed
cell death protein 1) blocker, and interleukin 15 (IL-15) to activate NK cells against AML.
Materials and Methods:
In this experimental study, the NK cells were isolated from mononuclear cells (MNCs) by
using magnetic activation cell sorting (MACS) and were activated using the different combinations of Hsp70, PD-1
blocker, and IL-15 and then followed by immunophenotyping, functional assays to estimate their killing potential, and
evaluation of expression pattern of
PRF1, PIK3CB, PD-1, AKT-1, FAS-L, TRAIL
, and
GER
A and B.
Results:
The expression of PD-1 was significantly (P<0.05) reduced after NK cell activation by the different formulas of
IL-15, Hsp70, and PD-1 blocker. The expression of NKG2A in the treated NK cells was reduced particularly in the IL-15
(P<0.01) and IL-15+PD-1 blocker (P<0.05) groups. The addition of Hsp70 increased its expression. The cytotoxic effect
of NK cells increased in all groups, especially in IL-15+PD-1 blocker besides increasing interferon-gamma (IFN-γ),
Granzymes, and perforin expression (P<0.05). All IL-15+PD-1 blocker group changes were associated with the upregulation
of
PIK3CB
and
AKT-1
as key factors of NK cell activation. The presence of Hsp70 reduced IFN-γ releasing,
and down-regulation of
PIK3CB, AKT-1
,
Granzymes
, and
Perforin
(P<0.05).
Conclusion:
We suggested the combination of IL-15 and PD-1 blocker could enhance the killing potential of AMLNK
cells. Moreover, Hsp70 in combination with IL-15 and PD-1 blocker interferes activation of AML-NK cells through
unknown mechanisms.
کلیدواژههای انگلیسی مقاله
Acute myeloid leukemia, Hsp70, Immunotherapy, Natural Killer Cells, PD-1
نویسندگان مقاله
Javad Firouzi |
Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
Abbas Hajifathali |
Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Masoumeh Azimi |
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
Neda Parvini |
Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Kurdistan, Iran
Fatemeh Ghaemi |
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
Niloufar Shayan Asl |
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
Amir Abbas Hedayati Asl |
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
Majid Safa |
Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
Marzieh Ebrahimi |
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
نشانی اینترنتی
https://www.celljournal.org/article_701725_40707905f9259e7c8f3cfe586f473723.pdf
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