Investigating the Multifaceted Impact of HIF-1 during Prostate Cancer and Its Potential Value as a Therapeutic Target
Technical Report,30 Sep 2014,29 Sep 2015
JOHNS HOPKINS UNIV BALTIMORE MD BALTIMORE United States
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Successful approaches to cancer immunotherapy require an understanding of the immune components in the microenvironment that enhance or inhibit tumor development and growth. Evidence is mounting that distinct T cell subsets contribute in positive or negative ways to these processes. An emerging area of interest relates to mechanisms by which sensing of metabolic cues regulates T cell fate and the character of the immune response. Our recent research suggested that an important metabolic regulator, hypoxia-inducible factor HIF -1, is a critical regulator of the balance between regulatory T cells Treg and Th17 cells, both of which play a role in inflammatory carcinogenesis and tumor immunity. These findings suggest that HIF-1 is likely to play an important role in cancer potentially through boosting tumor promoting T cells Th17. Thus, pharmacologic inhibition of HIF-1 in combination with therapies that target regulatory T cells may inhibit the two T cell types capable of promoting tumors or protecting them from eradication by the immune system. This project explores the efficacy by targeting the HIF-1 and Tregs in mouse cancer model. These experiments should provide new insights into the role of regulatory T cells and Th17 cells in cancer, and help us to design combination immunotherapy strategies that will be more successful in treating patients.