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Role of Hexokinase 2 in T Cell Metab...
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Mehta, Manan M.
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Role of Hexokinase 2 in T Cell Metabolism.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
Role of Hexokinase 2 in T Cell Metabolism./
作者:
Mehta, Manan M.
出版者:
Ann Arbor : ProQuest Dissertations & Theses, : 2020,
面頁冊數:
116 p.
附註:
Source: Dissertations Abstracts International, Volume: 80-07, Section: B.
Contained By:
Dissertations Abstracts International80-07B.
標題:
Cellular biology. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10937888
ISBN:
9780438764835
Role of Hexokinase 2 in T Cell Metabolism.
Mehta, Manan M.
Role of Hexokinase 2 in T Cell Metabolism.
- Ann Arbor : ProQuest Dissertations & Theses, 2020 - 116 p.
Source: Dissertations Abstracts International, Volume: 80-07, Section: B.
Thesis (Ph.D.)--Northwestern University, 2020.
This item must not be sold to any third party vendors.
T cells and cancer cells have many common features, including their need to proliferate and their metabolic requirements. In particular, glucose metabolism is highly upregulated in both cancer cells and T cells to support proliferation and other cellular functions. The first step of glycolysis is catalyzed by Hexokinase, which exists in 4 main isoforms. Hexokinase 2 (HK2) has been shown to be specifically upregulated in various types of cancers. Moreover, HK2 is required for tumor initiation, growth, and metastasis in different contexts. While this makes HK2 a potential target for cancer therapy, it is important to note that HK2 is also highly upregulated in T cells. It is unclear if inhibition of HK2 would adversely affect T cells by disrupting glucose metabolism. In the context of cancer therapy, T cell inhibition is not desirable, as it leaves patients susceptible to infections and could theoretically interfere with tumor immunity and potential immunotherapies. This thesis explores the necessity of HK2 in T cells in a variety of contexts. HK2 is largely dispensable for T cell activation, proliferation, and differentiation in vitro. In mouse models of inflammation and viral immunity, T cell function is mostly intact in the absence of HK2, with small differences in pathological inflammation. Suppressive T cell function is also spared in vivo when mice are deficient in HK2 in Regulatory T cells. Finally, we identify other potential metabolic difference between leukemic cancer cells and T cells. Together, the data show that HK2 functions mostly as a redundant enzyme in T cells and therefore it may serve as an attractive target for cancer therapy.
ISBN: 9780438764835Subjects--Topical Terms:
3172791
Cellular biology.
Role of Hexokinase 2 in T Cell Metabolism.
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T cells and cancer cells have many common features, including their need to proliferate and their metabolic requirements. In particular, glucose metabolism is highly upregulated in both cancer cells and T cells to support proliferation and other cellular functions. The first step of glycolysis is catalyzed by Hexokinase, which exists in 4 main isoforms. Hexokinase 2 (HK2) has been shown to be specifically upregulated in various types of cancers. Moreover, HK2 is required for tumor initiation, growth, and metastasis in different contexts. While this makes HK2 a potential target for cancer therapy, it is important to note that HK2 is also highly upregulated in T cells. It is unclear if inhibition of HK2 would adversely affect T cells by disrupting glucose metabolism. In the context of cancer therapy, T cell inhibition is not desirable, as it leaves patients susceptible to infections and could theoretically interfere with tumor immunity and potential immunotherapies. This thesis explores the necessity of HK2 in T cells in a variety of contexts. HK2 is largely dispensable for T cell activation, proliferation, and differentiation in vitro. In mouse models of inflammation and viral immunity, T cell function is mostly intact in the absence of HK2, with small differences in pathological inflammation. Suppressive T cell function is also spared in vivo when mice are deficient in HK2 in Regulatory T cells. Finally, we identify other potential metabolic difference between leukemic cancer cells and T cells. Together, the data show that HK2 functions mostly as a redundant enzyme in T cells and therefore it may serve as an attractive target for cancer therapy.
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