Date of Award

2012

Embargo Period

8-1-2024

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Microbiology and Immunology

College

College of Graduate Studies

First Advisor

M. Rita I. Young

Second Advisor

Amanda C. LaRue

Third Advisor

Terrence A. Day

Fourth Advisor

Julie A. Woolworth

Fifth Advisor

Xian-Kui (John) Zhang

Abstract

Head and neck cancer is the sixth most common cancer worldwide. Despite advances in diagnosis and treatment, the survival rates for patients with head and neck cancer have remained relatively unchanged for the past 30 years. Head and Neck Squamous Cell Carcinoma is a highly aggressive malignancy with a 5-year survival rate of only 50%. Of the patients diagnosed every year, 5% of head and neck squamous cell carcinoma (HNSCC) patients develop additional primary tumors, an effect that is thought to be associated with the high degree of immune suppression induced by the tumor. During the premalignant stage of HNSCC, there is an increase in the number of helper T subset Th17 cells, which then decreases in fully established HNSCC. The focus of our laboratory is on delineating the role of Th17 cells in HNSCC tumor development. Thus, the goal of this study is to elucidate the role of the tumor microenvironment in the decrease in Th17 cells observed in established HNSCC. We hypothesize that the decrease in Th17 cells is due to changes that occur in the tumor microenvironment during the transition from premalignant tissue to established HNSCC. To examine this, we characterized the cytokine levels in normal, premalignant and HNSCC tongue tissues. We also investigated the role of the microenvironment in the decrease in Th17 cell numbers observed in fully developed HNSCC compared to the premalignant stages. Our data showed an inflammatory response at the microenvironment which included both an increase in inflammatory cytokines as well as an increase in Th17 cells. This response was later attenuated during the HNSCC stage. When incubated with supernatant from premalignant tissue, Th17 cells maintained a higher level of IL-17 when compared to incubating with supernatant from control or HNSCC tissue. The opposite was found when splenocytes were incubated with these same supematants. The levels of IL-17 dropped when incubated with supernatant from premalignant tissue when compared to control or HNSCC.

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