Graduation Date

Summer 8-12-2022

Document Type

Thesis

Degree Name

Master of Science (MS)

Programs

Cancer Research

First Advisor

Kamiya Mehla

MeSH Headings

Macrophages, Pancreatic cancer, Immunosuppression, Spleen, Immune evasion

Abstract

Pancreatic cancer is currently the 3rd leading cause of all cancer-related deaths, with a 5-year survival rate remaining at 10%. The current standard treatment of care and a lack of effective diagnostic markers leaves patients with a dismal prognosis at advanced stages of the disease. This thesis research evaluated the effect of ApoE-expressing macrophages in the spleen. First, we aimed to assess the ApoE expression in the spleen of pancreatic tumor-bearing mice. Results showed that ApoE expression in splenic macrophages increased as the disease progressed. In addition, we saw a significant increase in marginal zone metallophilic macrophages and red pulp macrophages in the pancreatic tumor-bearing mice. The ApoE-/- pancreatic tumor-bearing mice showed a decrease in red pulp macrophages. Second, we aimed to understand the impact that ApoE expression in splenic macrophages would have on other immune cells in the spleen of pancreatic tumor-bearing mice. Our results showed an increased abundance of CD8+ T cells in the spleen of ApoE-/- pancreatic tumor-bearing mice. Also, the splenic CD8+ T cells displayed increased IFN-γ production in the absence of ApoE in the in vitro co-culture assay.

Moreover, we saw that ApoE-/- pancreatic tumor-bearing mice lived longer than their wild-type counterparts. These studies show that ApoE-expressing macrophages can impact the survival of pancreatic-tumor-bearing mice. Besides, our data show that ApoE-expressing macrophages can impair CD8+ T cell function in the splenic environment in PDAC tumor-bearing mice. Perhaps further evaluation of ApoE-expressing macrophages and their splenic subsets may help unravel the role of systemic immunosuppression and immune evasion in pancreatic cancer.

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