Exosomes are endosome derived secreted membrane vesicles within sizes ranging from 50nm to 100nm. They are secreted from viable cells varying from hematopoietic cells such as B lymphocytes and dendritic cells to non-hematopoietic cells such as intestinal epithelial cells, cortical neurons and tumor cells. Exosomes consist of a great number of membrane associated and cytosolic proteins; they are rich in membrane rafts and contains nucleic acid types such as mRNA, miRNA and DNA. This molecular complexity suggests that exosomes may carry out a variety of physiological functions via mediating intercellular communications. With the findings that cancer cells secrete great amount of exosomes compared to normal cells, it has become apparent that tumor exosomes may have functional implications especially on the tumor microenvironment. In this context, understanding the roles of tumor exosomes on cancer pathogenesis in large measure depends on revealing the interactions between the tumor exosomes and the immune system. Considering the host anti-tumor immunity, T lymphocytes constitute the major part of the adaptive immune responses generated against tumors.
In this study it was aimed to identify the gene expression profiles of T lymphocytes under the condition of tumor exosome treatments. For this aim Jurkat T cells, CD4+ T cell leukemia cells, was used as the T lymphocyte model. As the tumor exosome sources, ascitic fluids of patients with ovarian cancer were used. Tumor exosomes was isolated from ascitic fluids of ovarian cancer patients using gel filtration method. 106 Jurkat T cells were treated with 50µg of ascites derived tumor exosomes for one hour and three hour time periods. Control groups included untreated cells and cells treated with control exosomes. After tumor exosome treatment of Jurkat T cells, total RNA isolation and cDNA synthesis were performed. Expression of total of 84 genes involved in JAK-STAT signaling pathway was evaluated with real-time PCR using SYBR green method. ΔCt values were calculated and the fold changes of gene expression between experimental and control groups were determined.
As a result it was found that among the evaluated 84 genes, interleukin four (IL-4) gene expression was significantly up-regulated in tumor exosome treated Jurkat T cells in one hour but not three hour treatment time periods with compare to control groups.
Observing tumor exosome induced IL-4 gene expression in Jurkat T cells as early as one hour treatment time period suggests that tumor exosomes may up regulate IL-4 gene expression in Jurkat T cells via activation of receptor(s) expressed at the cell surface. Based on this cytokine-induction profile, tumor exosomes derived from ovarian cancer patients appears to lead to a Th2 biased response that has tumor promoting effects.
Citation Format: Ergin Sahin, Douglas D. Taylor, Cicek Gercel Taylor. Exosomes derived from ascitic fluid of patients with ovarian carcinoma induce IL-4 gene expression in T lymphocytes. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr B82.
- ©2015 American Association for Cancer Research.