Date of Completion
2024
Thesis Type
College of Arts and Science Honors
Department
Biological Sciences
First Advisor
Jon Boyson
Second Advisor
Melissa Pespeni
Keywords
gamma delta T cells, lung adenocarcinoma, PD-1, T regulatory cells
Abstract
gd T cells are a group of lymphocytes shown to be both antitumoral and tumor promoting. Previous research suggests that IL-17-producing gd T cells can promote tumorigenesis and metastasis while IFN-g-producing gd T cells suppress tumor growth. The mechanisms behind why these different gd T cell subsets have these opposing effects remains unclear. In this project, we used a mouse model of lung adenocarcinoma driven by the Kras oncoprotein and lacking the Stk11 tumor suppressor to examine the impact of gd T cells on the frequency, phenotype and functions of other immune cells in the lung tumor microenvironment. We consistently saw a decrease in the expression of inhibitory molecule PD-1 on CD4+ ab T cells when gd T cells were depleted from the lung. This downregulation of PD-1 may be specifically on T regulatory cells. We also saw a decrease in dendritic cells responsible for antigen presentation to these CD4+ T cells. Other immune cell types that may have been affected by a lack of gd T cells include neutrophils (some of which are myeloid derived suppressor cells) and NK cells. These results together suggest that gd T cells may be promoting tumor growth and metastasis in Kras-driven lung adenocarcinoma by inducing immunosuppressive mechanisms on surrounding cells.
Recommended Citation
Mathieu, Erin, "Characterization of the effects of gamma delta T cell depletion on Kras driven lung adenocarcinoma" (2024). UVM College of Arts and Sciences College Honors Theses. 147.
https://scholarworks.uvm.edu/castheses/147