Suppression of Dendritic Cell Maturation by Triple-Negative Breast Cancer Exosomes

Publication Date

July 2019

Location

LSU Health Medical Education Building

Document Type

Abstract

Start Date

26-7-2019 9:00 AM

End Date

26-7-2019 12:00 PM

Description

Exosomes are spherical membrane-enclosed nanoparticles released by cells that play a significant role in intercellular communication. The content of exosomes depends on the cell of origin and can include RNA and protein. After being released from their parental cell, exosomes are taken up by target cells and thus transfer their biological content causing a series of molecular changes. Cancer cells release significantly more exosomes and these exosomes have a unique composition relative to their normal counterparts. In addition, tumor-derived exosomes can rewire neighboring cells in order to create a tumor promoting microenvironment. Dendritic cells (DCs) are immune cells important in the host response to many diseases including infections and cancer. DCs function by presenting antigens on their outer cell membrane to T-cells which then activate and initiate a cytotoxic killing response. Immune cells including DCs are often suppressed during malignancy and are unable to induce tumor cell killing. The role of exosomes in the suppression of immune cells remains unclear. We hypothesize tumor-derived exosomes are responsible for the suppression of dendritic cell activation. In addition, we explore the effect of sulindac, a non-steroidal anti-inflammatory drug known to have anti-cancerous effects, on attenuating the ability of exosomes to suppress DC maturation. In this study we collected exosomes from the aggressive mouse murine triple-negative breast cancer cell line 4T1 and administered the exosomes into DC culture media. DC maturation was assessed using flow cytometry. Our results support our hypothesis and demonstrate tumor cell-derived exosomes can suppress the maturation of DCs. This study is significant because it provides insight into the involvement of exosomes in systemic and local malignancy-associated immune suppression and will aid future studies in developing treatment strategies to inhibit this process.

Comments

Mentors: Kristina Larter and Yaguang Xi, Department of Genetics, Stanley S. Scott Cancer Center

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Jul 26th, 9:00 AM Jul 26th, 12:00 PM

Suppression of Dendritic Cell Maturation by Triple-Negative Breast Cancer Exosomes

LSU Health Medical Education Building

Exosomes are spherical membrane-enclosed nanoparticles released by cells that play a significant role in intercellular communication. The content of exosomes depends on the cell of origin and can include RNA and protein. After being released from their parental cell, exosomes are taken up by target cells and thus transfer their biological content causing a series of molecular changes. Cancer cells release significantly more exosomes and these exosomes have a unique composition relative to their normal counterparts. In addition, tumor-derived exosomes can rewire neighboring cells in order to create a tumor promoting microenvironment. Dendritic cells (DCs) are immune cells important in the host response to many diseases including infections and cancer. DCs function by presenting antigens on their outer cell membrane to T-cells which then activate and initiate a cytotoxic killing response. Immune cells including DCs are often suppressed during malignancy and are unable to induce tumor cell killing. The role of exosomes in the suppression of immune cells remains unclear. We hypothesize tumor-derived exosomes are responsible for the suppression of dendritic cell activation. In addition, we explore the effect of sulindac, a non-steroidal anti-inflammatory drug known to have anti-cancerous effects, on attenuating the ability of exosomes to suppress DC maturation. In this study we collected exosomes from the aggressive mouse murine triple-negative breast cancer cell line 4T1 and administered the exosomes into DC culture media. DC maturation was assessed using flow cytometry. Our results support our hypothesis and demonstrate tumor cell-derived exosomes can suppress the maturation of DCs. This study is significant because it provides insight into the involvement of exosomes in systemic and local malignancy-associated immune suppression and will aid future studies in developing treatment strategies to inhibit this process.