Triple-negative breast cancer-derived exosomes change the immunological features of human monocyte-derived dendritic cells and influence T-cell responses

• Published in: Molecular biology reports 2024-12, Vol.51 (1), p.1058-1058, Article 1058
• Main Authors: Safaei, Sahar, Alipour, Shiva, Bahojb Mahdavi, Seyedeh Zahra, Shalmashi, Hooman, Shahgoli, Vahid Khaze, Shanehbandi, Dariush, Baradaran, Behzad, Kazemi, Tohid
• Format: Article
• Language: English
• Subjects: Animal Anatomy; Animal Biochemistry; Antigen (tumor-associated); Biomedical and Life Sciences; Breast cancer; breast neoplasms; breasts; Cancer therapies; cancer therapy; Cancer vaccines; Cancer Vaccines - immunology; Cell differentiation; Cell Differentiation - immunology; Cell Line, Tumor; coculture; Coculture Techniques; Cytokines; Cytokines - metabolism; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Enzyme-linked immunosorbent assay; Exosomes; Exosomes - immunology; Exosomes - metabolism; Female; Histology; Humans; Immunogenicity; Immunotherapy; Immunotherapy - methods; Leukocytes (mononuclear); Life Sciences; Lymphocyte Activation - immunology; Lymphocytes T; Monocytes; Monocytes - immunology; Monocytes - metabolism; Morphology; mRNA; Original Article; Peripheral blood mononuclear cells; Polymerase chain reaction; survival rate; T-lymphocytes; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Triple Negative Breast Neoplasms - immunology; Tumors; Vaccines
• ISSN: 0301-4851; 1573-4978; 1573-4978
• DOI: 10.1007/s11033-024-10007-8

Background Triple-negative breast cancer (TNBC) exhibits a lower survival rate in comparison to other BC subtypes. Utilizing dendritic cell (DC) vaccines as a form of immunotherapy is becoming a promising new approach to cancer treatment. However, inadequate immunogenicity of tumor antigens leads to unsatisfactory effectiveness of the DC vaccines. Exosomes are the basis for the latest improvements in tumor immunotherapy. This study examined whether TNBC-derived exosomes elicit immunogenicity on the maturation and function of monocyte-derived DCs and the impact of the exosome-treated monocyte-derived DCs (moDCs) on T cell differentiation. Methods exosomes were isolated from MDA-MB-231 TNBC cancer cells and characterized. Monocytes were separated from peripheral blood mononuclear cells and differentiated into DCs. Then, monocyte-derived DCs were treated with TNBC-derived exosomes. Furthermore, the mRNA levels of the genes and cytokines involved in DC maturation and function were examined using qRT-PCR and ELISA assays. We also cocultured TNBC-derived exosome-treated moDCs with T cells and investigated the role of the treatment in T cell differentiation by evaluating the expression of some related genes by qRT-PCR. The concentration of the cytokines secreted from T cells cocultured with exosome-treated moDCs was quantified by the ELISA assays. Results Our findings showed that TNBC-derived exosomes induce immunogenicity by enhancing moDCs’ maturation and function. In addition, exosome-treated moDCs promote cocultured T-cell expansion by inducing TH1 differentiation through increasing cytokine production. Conclusion TNBC-derived exosomes could improve vaccine-elicited immunotherapy by inducing an immunogenic response and enhancing the effectiveness of the DC vaccines. However, this needs to be investigated further in future studies.