Effect of Plasma-Derived Exosomes of Refractory/Relapsed or Responsive Patients with Diffuse Large B-Cell Lymphoma on Natural Killer Cells Functions

• Published in: Cell journal (Yakhteh) Vol. 22; no. 1; pp. 40 - 54
• Main Authors: Zare, Nasrin, Haghjooy Javanmard, S Haghayegh, Mehrzad, Valiollah, Eskandari, Nahid, Andalib, Ali Reza
• Format: Journal Article
• Language: English
• Published: Iran Royan Institute of Iran 01-04-2020; Royan Institute; Royan Institute (ACECR), Tehran
• Subjects: B-cell lymphoma; Cancer; CD16 antigen; CD69 antigen; Cell adhesion & migration; Cell cycle; Cell growth; Cell proliferation; Cytokines; Cytometry; Cytotoxicity; Diffuse Large B-Cell Lymphoma; Exosomes; Health risks; hsa-miR-155-5p; Interferon; Interferon-Gamma; Laboratories; Levels; Ligands; Lymphocytes B; Lymphoma; MicroRNAs; miRNA; Natural killer cells; NKG2 antigen; Original; Physiology; Plasma; Polymerase chain reaction; Proliferation; Proteins; Reverse transcription; Ships; Signal transduction; Toxicity; γ-Interferon; Iran; Cytotoxicity; Proliferation; Diffuse Large B-Cell Lymphoma; hsa-miR-155-5p; Interferon-Gamma
• ISSN: 2228-5806; 2228-5814
• DOI: 10.22074/cellj.2020.6550

The purpose of this study was to investigate effect of plasma-derived exosomes of refractory/relapsed or responsive diffuse large B-cell lymphoma (DLBCL) patients on natural killer (NK) cell functions.
In this cross-sectional and experimental study, NK cells were purified from responsive patients (n=10) or refractory/relapsed patients (n=12) and healthy donors (n=12). NK cells were treated with plasma-derived exosomes of responsive or refractory/relapsed patients. We examined the expression levels of
, hsalet- 7g-5p,
and
in NK cells quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Percentages of NK cells expressing CD69, NKG2D and CD16, NK cell cytotoxicity and NK cell proliferation (using flow-cytometry) as well as interferon-gamma (IFN-γ) level in the supernatant of NK cells using ELISA were also investigated.
We observed an increased level of
and a decreased level of
in NK cells treated with exosomes compared to untreated NK cell in healthy donors and DLBCL patients. An increase in
level was associated with an increased level of IFN-γ in healthy donors. The decreased levels of
were observed in NK cells treated with exosomes in comparison with untreated NK cells in DLBCL patients (P<0.05). There was no significant difference in the percentage of CD69
NK cells and NKG2D
NK cells in the absence or presence of exosomes of DLBCL patients in each group. Furthermore, we observed significant reduction of NK cell proliferation in DLBCL patients and healthy donors in the presence of exosomes of refractory/relapsed patients (P<0.05). A significant decrease was observed in cytotoxicity of NK cell in patients with DLBCL treated with exosomes of responsive patients.
Our findings demonstrated adverse effect of plasma-derived exosomes of DLBCL patients on some functions of NK cell. It was also determined that low NK cell count might be associated with impaired response to R-CHOP and an increased recurrence risk of cancer.