CML derived exosomes promote tumor favorable functional performance in T cells

BMC Cancer

Fariba Rad¹  Nazli Jafarzadeh²  Majid Sadeghizadeh²  Mohammad Ali Gholampour³  Saeideh Kavousi⁴  Mohammad-Reza Alivand⁵  Laleh Arzi⁶  Majid Pornour⁷ 

[1] Cellular and Molecular Research Center, Yasuj University of Medical Sciences;Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University;Department of Hematology, Faculty of Medical Science, Tarbiat Modares University;Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University;Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical sciences;Department of Microbiology, Shahr-e-Qods Branch, Islamic Azad University;Department of Photo Healing and Regeneration, Medical Laser Research Center, Yara Institute, ACECR;

关键词: Human primary cord blood T cell;    Chronic myelogenous leukemia (CML)-derived;    Exosomes;    Immunosuppression;    Tumor microenvironment;   

DOI  :  10.1186/s12885-021-08734-3

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown