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. 2017 Apr-Jun;19(1):137-145.
Epub 2016 Dec 21.

Adipose Derived Stem Cells Exert Immunomodulatory Effects on Natural Killer Cells in Breast Cancer

Behdokht Bahrami  1 , Ahmad Hosseini  2 , Abdol-Rasoul Talei  3 , Abbas Ghaderi  1 , Mahboobeh Razmkhah  2
Affiliations

Adipose Derived Stem Cells Exert Immunomodulatory Effects on Natural Killer Cells in Breast Cancer

Behdokht Bahrami et al. Cell J. 2017 Apr-Jun.

Abstract

Objective: Adipose derived stem cells (ASCs), as one of the important stromal cells in the tumor microenvironment, are determined with immunomodulatory effects. The principle aim of this study was to evaluate the immunosuppressive effects of ASCs on natural killer (NK) cells.

Materials and methods: In this experimental study, we assessed the expressions of indolamine 2, 3-dioxygenase (IDO1), IDO2 and human leukocyte antigen-G5 (HLA-G5) in ASCs isolated from breast cancer patients with different stages as well as normal individuals, using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Immunomodulatory effects of ASCs on the expression of CD16, CD56, CD69, NKG2D, NKp30, NKG2A and NKp44 was also assessed in peripheral blood lymphocytes (PBLs) by flow-cytometry.

Results: Our result showed that IDO1, IDO2 and HLA-G5 had higher mRNA expressions in ASCs isolated from breast cancer patients than those from normal individuals (P>0.05). mRNA expression of these molecules were higher in ASCs isolated from breast cancer patients with stage III tumors than those with stage II. The indirect culture of ASCs isolated from breast cancer patients and normal individuals with activated PBLs significantly reduced NKG2D+ and CD69+ NK cells (P<0.05).

Conclusion: Results of the present study suggest more evidences for the immunosuppression of ASCs on NK cells, providing conditions in favor of tumor immune evasion.

Keywords: Breast Cancer; Immunosuppression; Mesenchymal Stem Cells; NK Cells.

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Figures

Fig.1
Fig.1
Relative quantifications of IDO1, IDO2, and HLA-G in adipose derived stem cells (ASCs) of breast cancer patients and controls. Data were shown as the median of gene expression. P>0.05 for all genes.
Fig.2
Fig.2
Relative quantifications of IDO1, IDO2 and HLA-G5 in adipose derived stem cells (ASCs) of breast cancer patients with pathological stage II and stage III tumors. Data were shown as the median of gene expression. P>0.05 for all genes.
Fig.3
Fig.3
Relative quantifications of IDO1, IDO2, and HLA-G5 in adipose derived stem cells (ASCs) of breast cancer patients with stage III before and after co-culturing with PBLs. Data were shown as the median of gene expression. ***; P<0.001.
Fig.4
Fig.4
The schematic analysis of natural killer (NK) cell subpopulations among peripheral blood lymphocytes (PBLs). SSC versus FSC density plot, SSC versus PerCP-Cy5.5 and APC-labeled anti-CD3 versus FITC conjugated anti-CD16 fluorescence density plot.
Fig.5
Fig.5
Comparison of different populations of natural killer (NK) cells in the presence of cancer adipose derived stem cells (ASCs), normal ASCs and without ASCs.
Fig.6
Fig.6
SSC versus FSC density plot and the histogram representations of NKG2D, NKp44, NKp30, CD69 and NKG2A on natural killer (NK) cells by flow-cytometric analysis. Solid profiles represent expression of receptors and dashed histograms represent negative control.
Fig.7
Fig.7
Expression of activating and inhibitory natural killer (NK) receptors in the presence or absence of cancer or normal adipose derived stem cells (ASCs). Data were shown as mean ± SEM of cell percentages. *; P<0.05 and ***; P<0.01.
See this image and copyright information in PMC

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