Date of Graduation

5-2017

Document Type

Thesis

Degree Name

Bachelor of Science

Degree Level

Undergraduate

Department

Biological Sciences

Advisor

Zaharoff, David

Reader

Ivey, Mack

Second Reader

Henry, Ralph

Third Reader

Lessner, Daniel

Abstract

Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of cancer death among women in the United States (1). While treatments involving radiation and chemotherapy currently exist, disease must be detected early in order for the treatments to be somewhat effective, and there is no effective treatment after metastasis occurs (2). Additionally, current therapies do not mitigate tumor immunosuppression. Decreasing the tumor-associated immunosuppressive conditions while activating antitumor immunity could prevent recurrence and metastasis, possibly leading to an effective treatment for cancer (3). Tumor cell vaccines could possibly address this issue and have become a recent topic of research. They have the potential to generate tumor regression and antitumor immune responses, but they have had low clinical response rates and poor immunogenicity so far (3, 4).

We suspect the failure of cancer vaccines to be due to the immunosuppression and heterogeneity of breast cancers. Thus, to determine how and why different breast cancers induce different levels of immunosuppression, we studied different cancer cell lines of varying levels of immunogenicity. The study included five murine breast cancer cell lines, 4T1, 4T07, 66cl4, 168FARN, and 67NR. These are sister cell lines that were isolated from a Balb/cfC3H mouse and that differ in aggressiveness and metastatic capability. The production of immunosuppressive cytokines GM-CSF, G-CSF, M-CSF, IL-6, MCP-1, TGF-β, and VEGF was quantified for each of these cell lines. We also studied the effect these cytokines have on the expansion of myeloid-derived suppressor cells (MDSCs), which are known to suppress the immune response, and found that high levels of G-CSF are correlated with high numbers of MDSCs. A correlation between G-CSF levels and MDSC accumulation in these breast cancer cell lines could lead to future studies in which the effects of G-CSF are blocked in order to develop effective autologous breast cancer vaccines.

Keywords

breast cancer, oncology, vaccines, immunology