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Open Access 01-12-2021 | Leukemia | Research

CML derived exosomes promote tumor favorable functional performance in T cells

Authors: Nazli Jafarzadeh, Mohammad Ali Gholampour, Mohammad-Reza Alivand, Saeideh Kavousi, Laleh Arzi, Fariba Rad, Majid Sadeghizadeh, Majid Pornour

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

Leukemic cells facilitate the creation of the tumor-favorable microenvironment in the bone marrow niche using their secreted factors. There are not comprehensive details about immunosuppressive properties of chronic myelogenous leukemia-derived exosomes in the bone marrow stromal and immune compartment. We explained here that K562-derived exosomes could affect the gene expression, cytokine secretion, nitric oxide (NO) production, and redox potential of human primary cord blood-derived T cells (CB T cells).

Methods

Human primary cord blood-derived T cells were treated with K562-derived exosomes. We evaluated the expression variation of some critical genes activated in suppressor T cells. The alterations of some inflammatory and anti-inflammatory cytokines levels were assessed using ELISA assay and real-time PCR. Finally, NO production and intracellular ROS level in CB T cells were evaluated using Greiss assay and flow cytometry, respectively.

Results

Our results showed the over-expression of the genes involved in inhibitory T cells, including NQO1, PD1, and FoxP3. In contrast, genes involved in T cell activation such as CD3d and NFATc3 have been reduced significantly. Also, the expression of interleukin 10 (IL-10) and interleukin 6 (IL-6) mRNAs were significantly up-regulated in these cells upon exosome treatment. In addition, secretion of the interleukin 10, interleukin 6, and interleukin 17 (IL-17) proteins increased in T cells exposed to K562-derived exosomes. Finally, K562-derived exosomes induce significant changes in the NO production and intracellular ROS levels in CB T cells.

Conclusions

These results demonstrate that K562-derived exosomes stimulate the immunosuppressive properties in CB-derived T cells by inducing anti-inflammatory cytokines such as IL-10, reducting ROS levels, and arising of NO synthesis in these cells. Moreover, considering the elevation of FOXP3, IL-6, and IL-17 levels in these cells, exosomes secreted by CML cells may induce the fates of T cells toward tumor favorable T cells instead of conventional activated T cells.

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Title: CML derived exosomes promote tumor favorable functional performance in T cells
Authors: Nazli Jafarzadeh
Mohammad Ali Gholampour
Mohammad-Reza Alivand
Saeideh Kavousi
Laleh Arzi
Fariba Rad
Majid Sadeghizadeh
Majid Pornour
Publication date: 01-12-2021
Publisher: BioMed Central
Keyword: Leukemia
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08734-3

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Abstract

Background

Methods

Results

Conclusions

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