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.

Creator

• Mehta, Manan M

DOI

• https://doi.org/10.21985/n2-nqfx-eb74

Subject

• Cellular biology
• Immunology

Language

• en

Alternate Identifier

• etdadmin_upload_616623
• http://dissertations.umi.com/northwestern:14398

Keyword

• Hexokinase 2
• T Cell

Date created

• 2018-01-01

Resource type

• Dissertation

Rights statement

• In Copyright