Myeloid-Derived Suppressor Cell Acquisition of Antigen from Dendritic Cells and Induction of Antigen-Specific T Cell

Hannah Weber

Date of Award

2012

Document Type

Thesis

Degree Name

Bachelors

Department

Natural Sciences

First Advisor

Walstrom, Katherine

Keywords

Myeloid-Derived Suppressor Cells (MDSC), Immunology, Cancer

Area of Concentration

Biochemistry

Abstract

Myeloid-derived suppressor cell (MDSC)-induced suppression of tumor-specific T cells in an antigen-specific manner occurs in tumor-bearing mice and cancer patients. The mechanism by which MDSC obtain tumor antigens remains to be identified. We sought to elucidate this mechanism and evaluated our hypothesis that dendritic cells (DC) could provide antigens to peripheral lymphoid organ MDSC. We found that during an overnight co-culture DC previously loaded with ovalbumin (OVA) transferred OVA antigen to splenic MDSC, enabling re-isolated MDSC to suppress IFN-? release by activated OVA antigen-specific (OT-I) T cells in an ELISPOT. Addition of soluble factors derived from solid tumors to the co-culture abrogated the need for splenic MDSC to obtain OVA antigen from DC to suppress OT-I T cells. iNOS expression and arginase I expression and activity by splenic MDSC, associated with nonspecific suppression of activated T cells, increased with the presence of tumor-derived factors. This demonstrates that cytokines and growth factors present at the tumor site convert MDSC from antigen-specific to nonspecific suppressors in a dose-dependent manner. This study also demonstrates the ability of splenic MDSC to obtain antigens from DC, providing a potential mechanism by which peripheral lymphoid organ MDSC obtain tumor antigens in vivo. We plan to continue this study and determine the mechanism by which DC transfer antigens to splenic MDSC. Most importantly, we plan to validate our findings in tumor-bearing organisms. Elucidating the mechanism of peripheral lymphoid organ MDSC tumor antigen acquisition would aid in developing treatments that eliminate MDSC immunosuppression and promote anti-tumor immunity.

Rights

This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.

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