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Galectin-3 and the Modulation of Antitumor Immunity.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Galectin-3 and the Modulation of Antitumor Immunity./
作者:	Pucsek, Alexandra B.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2020,
面頁冊數:	109 p.
附註:	Source: Dissertations Abstracts International, Volume: 82-03, Section: B.
Contained By:	Dissertations Abstracts International82-03B.
標題:	Cellular biology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28068825
ISBN:	9798662431072

Galectin-3 and the Modulation of Antitumor Immunity.
Pucsek, Alexandra B.

Galectin-3 and the Modulation of Antitumor Immunity. - Ann Arbor : ProQuest Dissertations & Theses, 2020 - 109 p.

Source: Dissertations Abstracts International, Volume: 82-03, Section: B.

Thesis (Ph.D.)--The Johns Hopkins University, 2020.

This item must not be sold to any third party vendors.

In the last decade, galectin-3 has emerged as an important player in the development and progression of cancer, favoring immune suppression and dysfunction at disease sites. While this protein is a known tumor-promoting factor, its unique properties make the mechanisms of its functions difficult to study, and impede the development of therapies against it. Galectin-3 recognizes and binds β-galactoside carbohydrate residues through a highly-conserved C-terminal domain (CRD). It uniquely self-associates into homo-oligomers through a disordered N-terminal domain (NTD). We have previously shown that immune responses against galectin-3 are protective in pancreatic ductal adenocarcinoma (PDAC), and that its knockout in a mouse model of tumor tolerance improves effector function of antitumor CD8+ T cells and increases duration of tumor-free survival, suggesting a suppressive role for galectin-3 in antitumor immunity. The mechanisms of this suppression remain unknown.To learn whether galectin-3 could be a target for preventative therapeutics, I examined disease progression in a genetically engineered mouse model of PDAC development upon abrogation of galectin-3. I saw no significant change in lesion development or overall survival, indicating that galectin-3 is unlikely to be a good target for prevention strategies. In an effort to further study its mechanisms of immune suppression, I developed an assay to model galectin-3-mediated CD8+ T cell suppression, and showed that this assay allows successful activation of antigen-specific CD8+ T cells in vivo and detection of effector cytokines after re-stimulation in vitro. Through this assay we expect to learn how the discrete galectin-3 binding domains each impact its suppressive functions. Finally, I examined a transgenic mouse strain with a deficiency in dendritic cell populations, which regains those populations upon abrogation of galectin-3. This puzzling phenomenon remains unsolved, but I posit some lines of future inquiry that could elucidate this phenomenon, and inform our studies of galectin-3-mediated T cell modulation as well.Galectin-3 has been known as a factor in tumor permissiveness for decades, but has not yet been effectively targeted. Determining the mechanisms behind galectin-3-mediated immune cell modulation in the context of tumor will allow it to be targeted effectively, and could lead to better immunotherapeutic outcomes.

ISBN: 9798662431072Subjects--Topical Terms:

3172791
Cellular biology.
Subjects--Index Terms:

Galectin-3

Galectin-3 and the Modulation of Antitumor Immunity.
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