Document Type : Original Article

Authors

• Mahboobeh Razmkhah ¹
• Nadieh Abedi ¹
• Ahmad Hosseini ¹
• Mohammad Taghi Imani ²
• Abdol-Rasoul Talei ³
• Abbas Ghaderi ^{1, 4}

¹ Shiraz Institute for Cancer Research

² Department of Plastic Surgery

³ Department of Surgery

⁴ Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Background: Adipose derived stem cells (ASCs) provoke the accumulation and expansion of regulatory T cells, leading to the modulation of immune responses in tumor microenvironment.
Objective: To assess the effect of tumoral ASCs on the trend of regulatory T cells differentiation.
Methods: Peripheral blood naïve CD4+ T cells were co-cultured with ASCs derived from breast cancer or normal breast tissues. In separate cultures peripheral blood naïve CD4+ T cells were exposed to the culture supernatants of ASCs.
Results: Generation of CD4+CD25+Foxp3+ and CD4+CD25- Foxp3+ Treg subsets was observed after coculture of naïve CD4+ T cell with either ASCs or the related supernatant. The percentage of CD4+CD25+Foxp3+ cells increased after exposing naïve CD4+ T cells to both ASCs and their supernatants while augmentation of CD4+CD25-Foxp3+ subset mostly depended on the presence of ASCs. Similarly, upregulation of FoxP3 molecule was more significant in condition of cell to cell contact. IL-4 and IL-10 were up-regulated in the cocultured naïve CD4+ T cells after exposure to ASCs/supernatant while IFN-γ was down-regulated in the presence of ASCs.
Conclusion: Accordingly, ASC may act as one of the major players in tumor site with immunomodulatory effects, which may mostly be carried out through direct cellcell interaction.

Keywords

• Adipose Derived Stem Cell (ASC)
• Breast cancer
• Naïve CD4+ T Cell
• Regulatory T Cell
• Tumor Microenvironment