Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Pathology

Supervisor

Dr. Weiping Min

Abstract

Immunoinhibitory cell receptors that can induce a state of T cell exhaustion upon exposure to tumor antigen include Programmed Cell Death-1 (PD1). Although much research has been conducted on PD1, global miRNA regulation of PD1 in a cancer model has not been investigated. We hypothesized that miRNAs exist that can silence PD1 in vitro and revert symptoms of T cell exhaustion. Eleven miRNAs were discovered with altered expression between PD1+ and PD1- CD4+ T cells from melanoma-bearing mice. miR-28 and miR-107 mimics were shown to bind to and silence the 3’UTR of PD1, and miR-28, miR-150 and miR-107 inhibitors increased PD1 expression. Furthermore, no changes were observed in anti-CD3e induced proliferation, while miR-28 and miR-107 mimic transfection significantly reduced activation-induced apoptosis. This study is the first of its kind to discover global miRNA profiles in PD1+ T cells, providing novel targets for potential use as prognostic and therapeutic markers in melanoma.


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