Graduate Studies

 

First Advisor

Thomas M. Petro

Second Advisor

Audrey L. Atkin

Degree Name

Doctor of Philosophy (Ph.D.)

Committee Members

Eric Weaver, Greg Oakley, Jay Reddy

Department

Biological Sciences

Date of this Version

5-2025

Document Type

Dissertation

Citation

A dissertation presented to the faculty of the Graduate College at the University of Nebraska in partial fulfillment of requirements for the degree of Doctor of Philosophy

Major: Biological Sciences

Under the supervision of Professors Thomas M. Petro and Audrey Atkin

Lincoln, Nebraska, May 2025

Comments

Copyright 2025, Zachary P. Guinn. Used by permission

Abstract

Every year millions of people die from cancer throughout the world, and tens of millions of people are diagnosed with cancer worldwide. When surgery is not an option, treatment options commonly rely on the host immune system for optimal treatment efficacy. The expression of Interferon gamma (IFN-γ) by host immune cells is often associated with favorable antitumor immune responses. How IFN-γ is optimally induced in immune cells, and how IFN-γ promotes the transcription of genes downstream of the Interferon gamma receptor (IFNGR) is incompletely understood. Understanding how to induce immune cells to express optimal IFN-γ, and how the IFNGR induces optimal expression of genes could help in understanding how to effectively treat and eliminate cancer in patients. The research described in this dissertation describes how the transcription factor interferon regulatory factor 3 (IRF3) is essential for optimal expression of IFN-γ in response to tumor challenge. Additionally, these studies also describe an essential role for IRF3 for gene expression downstream of the IFNGR. Finally, this research describes how IFN-γ can reduce tumor cell viability, and how this viability can be further reduced through co-stimulation with the toll-like receptor 3 (TLR3) agonist polyinosinic-polycytidylic acid (Poly I:C), and how these effects rely on IRF3. Altogether, these results indicate that IRF3 is essential for optimal immune responses towards tumor challenge, and for optimal expression of anti-tumoral genes in tumor cells responding to IFN-γ stimulation.

Advisors: Thomas M. Petro and Audrey Aiken

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