Paediatric pre‐B acute lymphoblastic leukaemia‐derived exosomes regulate immune function in human T cells

Exosomes derived from solid tumour cells are involved in immune suppression, angiogenesis and metastasis; however, the role of leukaemia‐derived exosomes has less been investigated. Hence, changes in immune response‐related genes and human T cells apoptosis co‐incubated with exosomes isolated from p...

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Veröffentlicht in:Journal of cellular and molecular medicine 2022-08, Vol.26 (16), p.4566-4576
Hauptverfasser: Gholipour, Elham, Kahroba, Houman, Soltani, Nasim, Samadi, Parisa, Sarvarian, Parisa, Vakili‐Samiani, Sajjad, Hosein Pour Feizi, Abbas Ali, Soltani‐Zangbar, Mohammad Sadegh, Baghersalimi, Adel, Darbandi, Bahram, Movassaghpour, Aliakbar, Talebi, Mehdi, Motavalli, Roza, Mehdizadeh, Amir, Kazemi, Abdolhassan, Yousefi, Mehdi
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container_end_page 4576
container_issue 16
container_start_page 4566
container_title Journal of cellular and molecular medicine
container_volume 26
creator Gholipour, Elham
Kahroba, Houman
Soltani, Nasim
Samadi, Parisa
Sarvarian, Parisa
Vakili‐Samiani, Sajjad
Hosein Pour Feizi, Abbas Ali
Soltani‐Zangbar, Mohammad Sadegh
Baghersalimi, Adel
Darbandi, Bahram
Movassaghpour, Aliakbar
Talebi, Mehdi
Motavalli, Roza
Mehdizadeh, Amir
Kazemi, Abdolhassan
Yousefi, Mehdi
description Exosomes derived from solid tumour cells are involved in immune suppression, angiogenesis and metastasis; however, the role of leukaemia‐derived exosomes has less been investigated. Hence, changes in immune response‐related genes and human T cells apoptosis co‐incubated with exosomes isolated from patients' pre‐B cell acute lymphoblastic leukaemia were evaluated in this in vitro study. Vein blood sample was obtained from each newly diagnosed acute lymphoblastic leukaemia (ALL) patient prior any therapy. ALL serum exosomes were isolated by ultrafiltration and characterized using Western blotting and transmission electron microscopy. Exosomes were then co‐incubated with T lymphocytes and the gene expressions, as well as functions of human T cells were quantified by qRT‐PCR. Apoptosis and caspase‐3 and caspase‐9 protein expression were also evaluated by flowcytometry and Western blotting analysis, respectively. Exosomes isolated from ALL patients affected T lymphocytes and elevated the apoptosis. Moreover, these exosomes altered the T cells profile into regulatory type by increasing the expression of FOXP3 and Tregs‐related cytokines, including TGF‐B and IL‐10. The expression level of Th17‐related transcription factors (RoRγt) and interleukins (IL‐17 and IL‐23) decreased after this treatment. According to our findings, exosomes derived from ALL patients' sera carry immunosuppressive molecules, indicating the possible effect of exosomes as liquid biomarkers for cancer staging.
doi_str_mv 10.1111/jcmm.17482
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Hence, changes in immune response‐related genes and human T cells apoptosis co‐incubated with exosomes isolated from patients' pre‐B cell acute lymphoblastic leukaemia were evaluated in this in vitro study. Vein blood sample was obtained from each newly diagnosed acute lymphoblastic leukaemia (ALL) patient prior any therapy. ALL serum exosomes were isolated by ultrafiltration and characterized using Western blotting and transmission electron microscopy. Exosomes were then co‐incubated with T lymphocytes and the gene expressions, as well as functions of human T cells were quantified by qRT‐PCR. Apoptosis and caspase‐3 and caspase‐9 protein expression were also evaluated by flowcytometry and Western blotting analysis, respectively. Exosomes isolated from ALL patients affected T lymphocytes and elevated the apoptosis. Moreover, these exosomes altered the T cells profile into regulatory type by increasing the expression of FOXP3 and Tregs‐related cytokines, including TGF‐B and IL‐10. The expression level of Th17‐related transcription factors (RoRγt) and interleukins (IL‐17 and IL‐23) decreased after this treatment. According to our findings, exosomes derived from ALL patients' sera carry immunosuppressive molecules, indicating the possible effect of exosomes as liquid biomarkers for cancer staging.</description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/jcmm.17482</identifier><identifier>PMID: 35822529</identifier><language>eng</language><publisher>Chichester: John Wiley &amp; Sons, Inc</publisher><subject>Acute lymphoblastic leukemia ; Angiogenesis ; Antibodies ; Apoptosis ; Blood ; Cancer therapies ; Caspase ; CD8+ T cells ; Chemotherapy ; Exosomes ; Foxp3 protein ; Helper cells ; Hematology ; Immune system ; immunosuppression ; Interleukins ; Leukemia ; Lymphocytes ; Lymphocytes T ; Membranes ; Metastases ; mRNA ; Original ; Patients ; Proteins ; regulatory T cell ; Solid tumors ; Transcription factors ; Transmission electron microscopy ; tumour‐derived exosome ; Ultrafiltration ; Veins &amp; arteries ; Western blotting</subject><ispartof>Journal of cellular and molecular medicine, 2022-08, Vol.26 (16), p.4566-4576</ispartof><rights>2022 The Authors. published by Foundation for Cellular and Molecular Medicine and John Wiley &amp; Sons Ltd.</rights><rights>2022. 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subjects Acute lymphoblastic leukemia
Angiogenesis
Antibodies
Apoptosis
Blood
Cancer therapies
Caspase
CD8+ T cells
Chemotherapy
Exosomes
Foxp3 protein
Helper cells
Hematology
Immune system
immunosuppression
Interleukins
Leukemia
Lymphocytes
Lymphocytes T
Membranes
Metastases
mRNA
Original
Patients
Proteins
regulatory T cell
Solid tumors
Transcription factors
Transmission electron microscopy
tumour‐derived exosome
Ultrafiltration
Veins & arteries
Western blotting
title Paediatric pre‐B acute lymphoblastic leukaemia‐derived exosomes regulate immune function in human T cells
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