All ETDs from UAB

Advisory Committee Chair

Laurie F Harrington

Advisory Committee Members

John F Kearney

Jianmei W Leavenworth

Troy D Randall

Casey T Weaver

Document Type


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine


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.



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