Advisory Committee Chair
Laurie F Harrington
Advisory Committee Members
John F Kearney
Jianmei W Leavenworth
Troy D Randall
Casey T Weaver
Document Type
Dissertation
Date of Award
2021
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
CD4+ Foxp3+ regulatory T (Treg) cells are responsible for maintaining immunological homeostasis and self-tolerance through the regulation of immune responses against foreign and self-antigens, and they comprise both central Treg and effector Treg (eTreg) subsets. Because of their ability to suppress potent immune responses, eTreg cells expressing the transcription factor Blimp1 are frequently recruited to the tumor microenvironment (TME) to suppress anti-tumor responses by tumor infiltrating effector cells. Here, we demonstrate in murine transplantable tumor models that Blimp1 is required for intratumoral eTreg stability and that loss of Blimp1 by intratumoral eTreg cells results in their reduced suppressive activity and the acquisition of an effector phenotype. The impaired suppression by intratumoral eTreg cells leads to a reshaping of the TME and an increased anti-tumor cellular response, consisting of effector CD4, CD8, and NK cells. Additionally, loss of Blimp1 in a subset of eTreg cells known as T follicular regulatory (TFR) cells results in an increase in intratumoral T follicular helper (TFH) cells, germinal center B cells and IgE. The reprogramming of intratumoral eTreg cells along with the reshaping of the TME augments anti-tumor cellular and humoral immunity leading to a significant decrease in tumor growth and progression. Taken together, these results reveal the critical importance of Blimp1 to eTreg stability in the TME and highlight Blimp1 as a potential therapeutic target for reshaping the TME to control tumor.
Recommended Citation
Dixon, Michael, "The Impact of Blimp1 on eTreg Stability and the Tumor Microenvironment" (2021). All ETDs from UAB. 538.
https://digitalcommons.library.uab.edu/etd-collection/538