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


Nasrin Zare, Ph.D, 1Shaghayegh Haghjooy Javanmard, M.D, Ph.D., 2Valiollah Mehrzad, M.D, 3Nahid Eskandari, M.D, Ph.D., 1,*Alireza Andalib, Ph.D., 1
Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Department of Physiology, School of Medicine and Applied Physiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
Department of Hematology and Medical Oncology, Isfahan University of Medical Sciences, Isfahan, Iran
Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Department of Physiology, School of Medicine and Applied Physiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
Department of Hematology and Medical Oncology, Isfahan University of Medical Sciences, Isfahan, Iran
*Corresponding Address: P.O.Box: 81746-73461 Department of Immunology School of Medicine Isfahan University of Medical Sciences Isfahan Iran Email:neskandari@med.mui.ac.ir
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Abstract

Objective

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.

Materials and Methods

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 hsa-miR-155-5p, hsa- let-7g-5p, INPP5D (SHIP-1) and SOCS-1 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.

Results

We observed an increased level of hsa-miR-155-5p and a decreased level of SOCS-1 in NK cells treated with exosomes compared to untreated NK cell in healthy donors and DLBCL patients. An increase in hsa-miR-155-5p level was associated with an increased level of IFN-γ in healthy donors. The decreased levels of hsa-let-7g-5p 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.

Conclusion

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.